Publications

Author	Title	Year	Journal/Proceedings	Reftype
Babcock, M. S. & Olson, W. K.	The effect of mathematics and coordinate system on comparability and ependenciesof nucleic acid structure parameters. [Abstract] [BibTeX]	1994	Journal of Molecular Biology	article
Abstract: This paper critically examines the methodologies used to analyze nucleic acid three-dimensional structure based on guidelines set at a 1988 EMBO workshop. The implications of these analyses cannot be fully understood without a thorough knowledge of how the nos. are calcd. This paper addresses one aspect of the calcns., namely the obsd. correlations between various parameters. These correlations are addressed in the mathematics by explicitly incorporating the concept of a pivot point, which is the point about which a base rotates as it buckles, propeller twists and opens. Pivot points enable one to model the phys. motion of bases more accurately. As a result, they greatly reduce and/or eliminate the statistical correlations between rotational and translational parameters found in other approaches. The correlations that are reduced or eliminated are actually artifacts of the mathematics employed and do not reflect true structural properties of nucleic acids. The mathematics the authors have developed, including the mathematics of pivot points, are presented in the companion paper. Here, the authors explain how some of the obsd. correlations occur as a byproduct of the method of calcn., while others are truly structural, and the authors show how optimum pivot points can be detd. to minimize artifactual correlations. The observation that exptl. bases often rotate about the long axis in a ropellermotion as well as rotate about the Z-axis of each base, öpeninginto the major groove, is evident in the location of the optimum region for the pivot point as detd. in this study. The authors consider locating a pivot point as a calibration step to increase the agreement between phys. intuition and the mathematics of the authors' program. [on SciFinder (R)]
BibTeX: @article{RefWorks:431, author = {Marla S. Babcock and Wilma K. Olson}, title = {The effect of mathematics and coordinate system on comparability and \"dependencies\" of nucleic acid structure parameters.}, journal = {Journal of Molecular Biology}, year = {1994}, volume = {237}, number = {1}, pages = {98-124}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 3, 6; CODEN: JMOBAK; CAS Registry Numbers: 65-71-4 (Thymine); 71-30-7 (Cytosine); 73-24-5 (Adenine); 73-40-5 (Guanine) Role: PRP (Properties) (structure of, calcn. of, effect of mathematics and coordinate system on)} }
Babcock, M. S., Pednault, E. P. D. & Olson, W. K.	Nucleic acid structure analysis. Mathematics for local cartesian and helical structure parameters that are truly comparable between structures. [Abstract] [BibTeX]	1994	Journal of Molecular Biology	article
Abstract: Analyzing nucleic acid structures in a comparable manner has become increasingly important as the no. of solved structures had increased. This paper presents the concepts, mathematics, theorems, and proofs that form the basis of a new program to analyze three-dimensional DNA and RNA structures. The approach taken here provides numerical data in accordance with guidelines set at a 1988 EMBO workshop. Math. definitions are provided for all local structural parameters described in the guidelines. The definitions satisfy the guideline requirements while preserving the original phys. intuition of the parameters. In particular, the rotational parameters are true rotations based on a simple phys. model (net rotation at const. angular velocity), not Euler angles or angles between vectors and planes as is the case with other approaches. As a result, the math. definitions are sym. with the property that a 5 Deg tilt is the same as a 5 Deg roll and a 5 Deg twist, except that the rotations take place about different axes. In other approaches, a 5 Deg tilt can mean a different amt. of net rotation than a 5 Deg roll or a 5 Deg twist. A second unique feature of the mathematics is that it explicitly incorporates the concept of a pivot point, which is the point about which a base in a base-pair rotates as it buckles, propeller twists, and opens. Pivot points enable one to model the phys. motion of bases more accurately. As a result, they greatly reduce and/or eliminate the statistical correlations between rotational and translational parameters that arise as math. induced artifacts in other approaches. This paper, together with the statistical anal. in the companion paper for detg. the locations of the pivot points, provides everything needed to understand the output of the program as it relates to individual structures. [on SciFinder (R)]
BibTeX: @article{RefWorks:430, author = {Marla S. Babcock and Edwin P. D. Pednault and Wilma K. Olson}, title = {Nucleic acid structure analysis. Mathematics for local cartesian and helical structure parameters that are truly comparable between structures.}, journal = {Journal of Molecular Biology}, year = {1994}, volume = {237}, number = {1}, pages = {125-156}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 3, 6; CODEN: JMOBAK} }
Babcock, M. S., Pednault, E. P. D. & Olson, W. K.	Nucleic acid structure analysis: a users guide to a collection of new analysis programs. [Abstract] [BibTeX]	1993	Journal of Biomolecular Structure & Dynamics	article
Abstract: Common nomenclature describing the geometry of nucleic acid structures was established at a 1988 EMBO Workshop on DNA Curvature and Bending [Diekmann, S. (1988); Diekmann, S. (1989); Sarma, R.H. (1988); Dickerson, R. E. (1989); Dickerson, R. E. et al. (1989)]. The authors have subsequently developed and incorporated sophisticated mathematics in a computer program to calc. the parameters described by the guidelines. The program calcs. all the local parameters relating complementary bases and neighboring base and base pairs in both Cartesian and helical coordinate frames. In addn., the main math. property requested by the EMBO guidelines - that the magnitude of the parameters be independent of strand or direction of measurement - is accomplished without the use of a midway coordinate frame for the rotational parameters. The mathematics preserve the phys. intuition used in defining the parameters; in particular, the rotational parameters are true rotations based on a simple phys. model (rotation at const. angular velocity for a unit amt. of time), not Euler angles or angles between vectors and planes as is the case with other approaches. As a result, the math. equations are sym. with the property that a 5 Deg tilt is the same as a 5 Deg roll or a 5 Deg twist, except that the rotations take place about different axes. In other approaches, a 5 Deg tilt can mean a different amt. of net rotation from a 5 Deg roll or a 5 Deg twist. In addn., a great deal of flexibility is built into the program so that the user has control over the anal., including the input format, the coordinate frame used for the base pairing relationship, the point about which the rotations are performed, and which geometric relationships are analyzed. While there is a great deal of flexibility, the program is easy to use. Interactive queries and user accessible files make the options in the program very convenient to tailor to individual needs. In addn., there is also a program that calcs. bond lengths, valence angles, and torsion angles along the nucleic acid backbone, and within the sugar and base rings. Another program 'learns' the identities of the bond lengths, valence angles, and torsion angles that the user would like to det. This last program is esp. useful for calcg. the hydrogen bonds between atoms in complementary strands as well as the unusual hydrogen bonds found in recently detd. nucleic acid NMR structures or within protein/nucleic acid complexes. [on SciFinder (R)]
BibTeX: @article{RefWorks:307, author = {Marla S. Babcock and Edwin P. D. Pednault and Wilma K. Olson}, title = {Nucleic acid structure analysis: a users guide to a collection of new analysis programs.}, journal = {Journal of Biomolecular Structure & Dynamics}, year = {1993}, volume = {11}, number = {3}, pages = {597-628}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 6; CODEN: JBSDD6} }
Benevides, J. M., Chan, G., Lu, X., Olson, W. K., Weiss, M. A. & Thomas, G. J.	Protein-Directed DNA Structure. I. Raman Spectroscopy of a High-Mobility-Group Box with Application to Human Sex Reversal. [Abstract] [BibTeX]	2000	Biochemistry	article
Abstract: Protein-directed reorganization of DNA underlies mechanisms of transcription, replication, and recombination. A mol. model for DNA reorganization in the regulation of gene expression is provided by the sequence-specific high-mobility-group (HMG) box. Structures of HMG-box complexes with DNA are characterized by expansion of the minor groove, sharp bending toward the major groove, and local unwinding of the double helix. The Raman vibrational signature of such DNA reorganization has been identified in a study of the SRY HMG box, encoded by the human male-detg. region of the Y chromosome. The authors observe in the human SRY-HMG:DNA complex extraordinarily large perturbations to Raman bands assocd. with vibrational modes of the DNA backbone and accompanying large increases in intensities of Raman bands attributable to base unstacking. In contrast, DNA major-groove binding, as occurs for the bZIP protein GCN4 [Benevides, J. M., Li, T., Lu, X.-J., Srinivasan, A. R., Olson, W. K., Weiss, M. A., and Thomas, G. J., Jr. (2000) Biochem. 39, XXX-XXX], perturbs the Raman signature of DNA only marginally. Raman markers of minor-groove recognition in the human SRY-HMG:DNA complex are due primarily to perturbation of specific vibrational modes of deoxyribose moieties and presumably reflect desolvation at the nonpolar interface of protein and DNA. These Raman markers may be diagnostic of protein-induced DNA bending and are proposed as a baseline for comparative anal. of mutations in SRY that cause human sex reversal. [on SciFinder (R)]
BibTeX: @article{RefWorks:391, author = {James M. Benevides and Ging Chan and Xiang-Jun Lu and Wilma K. Olson and Michael A. Weiss and George J. Thomas}, title = {Protein-Directed DNA Structure. I. Raman Spectroscopy of a High-Mobility-Group Box with Application to Human Sex Reversal.}, journal = {Biochemistry}, year = {2000}, volume = {39}, number = {3}, pages = {537-547}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 3-4; CA Section Cross-references: 6; CODEN: BICHAW; CAS Registry Numbers: 257616-53-8 Role: BPR (Biological process), BSU (Biological study, unclassified), BIOL (Biological study), PROC (Process) (Raman spectroscopy of SRY high-mobility-group Box:DNA complex and possible application to diagnosis of human sex reversal)} }
Benevides, J. M., Li, T., Lu, X., Srinivasan, A. R., Olson, W. K., Weiss, M. A. & Jr, G. J. T.	Protein-Directed DNA Structure II. Raman Spectroscopy of a Leucine Zipper bZIP Complex. [Abstract] [BibTeX]	2000	Biochemistry	article
Abstract: Mechanisms of transcription may involve protein-directed changes in DNA structure and DNA-directed changes in protein structure. We have employed Raman spectroscopy to characterize vibrational signatures assocd. with such induced mol. fitting for two classes of transcription factors-the basic leucine-zipper (bZIP) motif and the high-mobility-group (HMG) box-each with a DNA target site. Results for bZIP are described here; findings for the HMG-box are reported in the preceding paper in this issue [Benevides, J. M., Chan, G., Lu, X.-J., Olson, W. K., Weiss, M. A., and Thomas, G. J., Jr. (2000) Biochem. 39]. The yeast activator GCN4 provides a well-studied example of bZIP recognition, wherein B-DNA serves essentially as a template for protein folding. Anal. of Raman spectra of the 57-residue GCN4 bZIP domain, its AP-1 binding site, and their specific complex confirms a DNA-induced increase in a-helicity, attributable to folding of GCN4 basic arms with virtually no change in B-DNA structure, consistent with previous X-ray and NMR structure detns. The absence of DNA perturbations in the bZIP model contrasts sharply with the HMG box, where DNA structure perturbations predominate. The bZIP and HMG-box models represent two opposing extremes in a range of induced fits identifiable by Raman spectroscopy. Previously characterized l repressor/operator complexes [Benevides, J. M., Weiss, M. A., and Thomas, G. J. (1994) J. Biol. Chem. 269, 10869-10878] occupy an intermediate position within this range. A comprehensive tabulation of Raman markers proposed as diagnostic of different protein/DNA recognition motifs is presented. The results are analyzed in terms of available DNA crystal structures (Nucleic Acid Database) to identify details of DNA conformation that correlate with specific Raman recognition markers. [on SciFinder (R)]
BibTeX: @article{RefWorks:390, author = {James M. Benevides and Tiansheng Li and Xiang-Jun Lu and A. R. Srinivasan and Wilma K. Olson and Michael A. Weiss and George J. Thomas Jr}, title = {Protein-Directed DNA Structure II. Raman Spectroscopy of a Leucine Zipper bZIP Complex.}, journal = {Biochemistry}, year = {2000}, volume = {39}, number = {3}, pages = {548-556}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-7; CODEN: BICHAW} }
Berman, H. M., Clowney, L., Gelbin, A., Hsieh, S., Olson, W. K., Westbrook, J. & Zardecki, C.	The nucleic acid database: a research tool for the study of nucleic acid crystal structures. [BibTeX]	1996	Folding & design	article
BibTeX: @article{RefWorks:411, author = {Helen M. Berman and Lester Clowney and Anke Gelbin and Shu-Hsin Hsieh and Wilma K. Olson and John Westbrook and Christine Zardecki}, title = {The nucleic acid database: a research tool for the study of nucleic acid crystal structures.}, journal = {Folding & design}, year = {1996}, volume = {1}, number = {Suppl.}, pages = {S10}, note = {Copyright (C) 2007 ACS on SciFinder (R)); CODEN: FODEFH} }
Berman, H. M., Olson, W. K., Beveridge, D. L., Westbrook, J., Gelbin, A., Demeny, T., Hsieh, S. H., Srinivasan, A. R. & Schneider, B.	The nucleic acid database. A comprehensive relational database of three-dimensional structures of nucleic acids. [Abstract] [BibTeX]	1992	Biophysical journal	article
Abstract: A description is given of the Nucleic Acid Database which contains information on 192 DNA and RNA crystal structures, including 130 entries having at coordinates. Data prepn., database management, and information retrieval are described. [on SciFinder (R)]
BibTeX: @article{RefWorks:317, author = {Helen M. Berman and Wilma K. Olson and David L. Beveridge and John Westbrook and Anke Gelbin and Tamas Demeny and Shu Hsin Hsieh and A. R. Srinivasan and Bohdan Schneider}, title = {The nucleic acid database. A comprehensive relational database of three-dimensional structures of nucleic acids.}, journal = {Biophysical journal}, year = {1992}, volume = {63}, number = {3}, pages = {751-759}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 20-5; CA Section Cross-references: 6; CODEN: BIOJAU} }
Boschitsch, A. H., Fenley, M. O. & Olson, W. K.	A Fast Adaptive Multipole Algorithm for Calculating Screened Coulomb (Yukawa) Interactions. [Abstract] [BibTeX]	1999	Journal of Computational Physics	article
Abstract: The screened Coulomb (Yukawa or Debye-Huckel) potential, F=exp(-kr)/r, where r is the sepn. distance and k is the Debye-Huckel screening parameter, gives a good description of the electrostatic interactions in a variety of biol. and phys. important charged systems. It is well known that the direct calcn. of the energy and forces due to a collection of N charged particles involves the pairwise summation of all charged particle interactions and exhibits an O(N2) computational complexity which severely restricts max. problem size. This has prompted the development of fast summation algorithms that allow the electrostatic energy and forces to be obtained in only O(N log N) operations. To date, however, practically all such implementations have been limited exclusively to pure Coulombic potentials (k=0), and the central contribution of the present method is to extend this capability to the entire range of the inverse Debye length, k>=0. The basic formulation and computational implementation of the spherical modified Bessel function-based multipole expansions appropriate for the screened Coulomb kernel are first presented. Next, a simple model system consisting of a single source charged particle is studied to show that the max. electrostatic energy error incurred by an M-order multipole expansion for the Yukawa potential is bounded above by the error of the equiv. multipole expansion for the Coulombic potential. Finally, timing and accuracy studies are presented for a variety of charged systems including polyelectrolyte chains, random distributions of charges inside a cube, and face-centered-cubic lattice charge configurations contg. up to 103,823 charges. (c) 1999 Academic Press. [on SciFinder (R)]
BibTeX: @article{RefWorks:396, author = {Alexander H. Boschitsch and Marcia O. Fenley and Wilma K. Olson}, title = {A Fast Adaptive Multipole Algorithm for Calculating Screened Coulomb (Yukawa) Interactions.}, journal = {Journal of Computational Physics}, year = {1999}, volume = {151}, number = {1}, pages = {212-241}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 65; CODEN: JCTPAH} }
Chalikian, T. V., Volker, J., Srinivasan, A. R., Olson, W. K. & Breslauer, K. J.	The hydration of nucleic acid duplexes as assessed by a combination of volumetric and structural techniques. [Abstract] [BibTeX]	1999	Biopolymers	article
Abstract: Using high precision densimetric and ultrasonic measurements, we have detd., at 25 Deg, the apparent molar volumes jV and the apparent molar compressibilities jKs of four nucleic acid duplexes-namely, the DNA duplex, poly(dIdC).poly(dIdC); the RNA duplex, poly(rA).poly(rU); and the two DNA/RNA hybrid duplexes, poly(rA).poly(dT) and poly(dA).poly(rU). Using available fiber diffraction data on these duplexes, we have calcd. the mol. vols. as well as the solvent-accessible surface areas of the constituent charged, polar, and nonpolar at. groups. We found that the hydration properties of these nucleic acid duplexes do not correlate with the extent and the chem. nature of the solvent-exposed surfaces, thereby suggesting a more specific set of duplex-water interactions beyond general solvation effects. A comparative anal. of our volumetric data on the four duplexes, in conjunction with available structural information, suggests the following features of duplex hydration: (a) The four duplexes exhibit different degrees of hydration, in the order poly(dIdC).poly(dIdC) > poly(dGdC).poly(dGdC) > poly(dAdT).poly(dAdT) ~ poly(dA).poly(dT). (b) Repetitive AT and IC sequences within a duplex are solvated beyond general effects by a spine of hydration in the minor groove, with this sequence-specific water network involving about 8 addnl. water mols. from the second and, perhaps, even the third hydration layers. (c) Repetitive GC and IC sequences within a duplex are solvated beyond general effects by a atch of hydrationin the major groove, with this water network involving about 13 addnl. water mols. from the second and, perhaps, even the third hydration layers. (d) Random sequence, polymeric DNA duplexes, which statistically lack extended regions of repetitive AT, GC, or IC sequences, do not experience such specific enhancements of hydration. Consequently, consistent with our previous observations (T. V. Chalikian et al., 1994), duplexes with approx. 50% AT content exhibit the weakest hydration, while an increase or decrease from this AT content causes enhancement of hydration, either due to stronger hydration of the minor groove (an increase in AT content) or due to stronger hydration of the major groove (an increase in GC content). (e) In dil. aq. solns., a B-DNA duplex is more hydrated than an A-DNA duplex, a volumetric-based conclusion that is in agreement with previous results obtained on crystals, fibers, and DNA solns. in org. solvent-water mixts. (f) the A-like, RNA duplex poly(rA).poly(rU) and the structurally similar A-like, hybrid duplex poly(rA).poly(dT), exhibit similar hydration properties, while the structurally distinct A-like, hybrid duplex poly(rA).poly(dT) and non-A-like, hybrid duplex poly(dA).poly(rU) exhibit differential hydration properties, consistent with structural features dictating hydration characteristics. We discuss how volumetric characterizations, in conjunction with structural studies, can be used to describe, define, and resolve the general and sequence/conformation-specific hydration properties of nucleic acid duplexes. [on SciFinder (R)]
BibTeX: @article{RefWorks:393, author = {Tigran V. Chalikian and Jens Volker and A. R. Srinivasan and Wilma K. Olson and Kenneth J. Breslauer}, title = {The hydration of nucleic acid duplexes as assessed by a combination of volumetric and structural techniques.}, journal = {Biopolymers}, year = {1999}, volume = {50}, number = {5}, pages = {459-471}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BIPMAA; CAS Registry Numbers: 24936-38-7; 27156-07-6 (Poly(rA).poly(dT); 33572-75-7 (Poly(dA).poly(rU); 34639-43-5 Role: BSU (Biological study, unclassified), PRP (Properties), BIOL (Biological study) (hydration of nucleic acid duplexes as assessed by combination of volumetric and structural techniques)} }
Clowney, L., Jain, S. C., Srinivasan, A. R., Westbrook, J., Olson, W. K. & Berman, H. M.	Geometric Parameters in Nucleic Acids: Nitrogenous Bases. [Abstract] [BibTeX]	1996	Journal of the American Chemical Society	article
Abstract: Estd. bond-lengths and bond-angle parameters for the nitrogenous base side groups of nucleic acids are presented. These values are the result of a statistical survey of small mols. in the Cambridge Structural Database for which high-resoln. X-ray and neutron crystal structures are available. The statistics include arithmetic means and std. deviations for the different samples, as well as comparisons of the population distributions for sugar- and non-sugar-derivatized bases. These accumulated data provide appropriate target values for refinements of oligonucleotide structures, as well as sets of std. at. coordinates for the five common bases. [on SciFinder (R)]
BibTeX: @article{RefWorks:417, author = {Lester Clowney and Shri C. Jain and A. R. Srinivasan and John Westbrook and Wilma K. Olson and Helen M. Berman}, title = {Geometric Parameters in Nucleic Acids: Nitrogenous Bases.}, journal = {Journal of the American Chemical Society}, year = {1996}, volume = {118}, number = {3}, pages = {509-518}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 26-9; CA Section Cross-references: 22, 75; CODEN: JACSAT; CAS Registry Numbers: 65-71-4 (Thymine); 66-22-8 (Uracil); 71-30-7 (Cytosine); 73-24-5 (Adenine); 73-40-5 (Guanine); 18444-01-4 (Adenine conjugate monoacid); 20791-98-4 (Cytosine conjugate monoacid) Role: PRP (Properties) (statistical analyses of bond lengths and valence angles for neutral and protonated purine and pyrimidine bases)} }
Coleman, B. D., Olson, W. K. & Swigon, D.	Theory of sequence-dependent DNA elasticity. [Abstract] [BibTeX]	2003	Journal of Chemical Physics	article
Abstract: The elastic properties of a mol. of duplex DNA are strongly dependent on nucleotide sequence. In the theory developed here the contribution yn of the nth base-pair step to the elastic energy is assumed to be given by a function y~n of six kinematical variables, called tilt, roll, twist, shift, slide, and rise, that describe the relative orientation and displacement of the nth and (n+1)th base pairs. The sequence dependence of elastic properties is detd. when one specifies the way y~n depends on the nucleotides of the two base pairs of the nth step. Among the items discussed are the symmetry relations imposed on y~n by the complementarity of bases, i.e., of A to T and C to G, the antiparallel nature of the DNA sugar-phosphate chains, and the requirement that y~n be independent of the choice of the direction of increasing n. Variational equations of mech. equil. are here derived without special assumptions about the form of the functions y~n, and numerical solns. of those equations are shown for illustrative cases in which y~n is, for each n, a quadratic form and the DNA forms a closed, 150 base-pair, minicircle that can be called a DNA o-ring because it has a nearly circular stress-free configuration. Examples are given of noncircular equil. configurations of naked DNA o-rings and of cases in which the interaction with ligands induces changes in configuration that are markedly different from those undergone by a minicircle of intrinsically straight DNA. When a minicircle of intrinsically straight DNA interacts with an intercalating agent that upon binding to DNA causes a local redn. of intrinsic twist, the configuration that minimizes elastic energy depends on the no. of intercalated mols., but is independent of the spatial distribution of those mols. along the minicircle. In contrast, it is shown here that the configuration and elastic energy of a DNA o-ring can depend strongly on the spatial distribution of the intercalated mols. As others have obsd. in calcns. for Kirchhoff rods with intrinsic curvature, an o-ring that has its intrinsic twist reduced at a single base-pair step can undergo large deformations with localized untwisting and bending at remote steps, even when the amt. a of twist redn. is less than the amt. required to induce supercoiling in rings of intrinsically straight DNA. We here find that the presence in the functions y~n of cross-terms coupling twist to roll can amplify the configurational changes induced by local untwisting to the point where there can be a value of a at which a first-order transition occurs between two distinct stable noncircular configurations with equal elastic energy. [on SciFinder (R)]
BibTeX: @article{RefWorks:377, author = {Bernard D. Coleman and Wilma K. Olson and David Swigon}, title = {Theory of sequence-dependent DNA elasticity.}, journal = {Journal of Chemical Physics}, year = {2003}, volume = {118}, number = {15}, pages = {7127-7140}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CA Section Cross-references: 65; CODEN: JCPSA6} }
Czapla, L., Swigon, D. & Olson, W. K.	Sequence-Dependent Effects in the Cyclization of Short DNA. [Abstract] [BibTeX]	2006	Journal of Chemical Theory and Computation	article
Abstract: A new, computationally efficient Monte Carlo approach has been developed to est. the ring-closure properties of short, realistically modeled DNA chains. The double helix is treated at the level of base-pair steps using an elastic potential that accounts for the sequence-dependent variability in the intrinsic structure and elastic moduli of the base-pair steps, including the known coupling of conformational variables. Rather than using traditional Metropolis-Monte Carlo techniques to generate representative configurations, a Gaussian sampling method is introduced to construct three-dimensional structures from linear combinations of the rigid-body parameters defining the relative orientation and displacement of successive base pairs. The computation of the J factor, the well-known ratio of the equil. consts. for cyclization vs bimol. assocn. of a linear mol., takes into account restrictions on the displacement and directions of the base pairs joined in ring closure, including the probability that the end-to-end vector is null and the terminal base pairs coincide. The increased sample sizes needed to assess the likelihood that very short chains satisfy these criteria are attained using the Alexandrowicz half-chain sampling enhancement technique in combination with selective linkage of the two-half-chain segments. The method is used to investigate the cyclization properties of arbitrary-length DNA with greatly enhanced sampling sizes, i.e., O(1014) configurations, and to est. J factors lower than 0.1 pM with high accuracy. The methodol. has been checked against classic theor. predictions of the cyclization properties of an ideal, inextensible, naturally straight, DNA elastic rod and then applied to investigate the extent to which one can account for the unexpectedly large J factors of short DNA chains without the need to invoke significant distortions of double helical structure. Several well-known structural features of DNA-including the presence of intrinsic curvature, roll-twist coupling, or enhanced pyrimidine-purine deformability-bring the computed J factors in line with the obsd. data. Moreover, periodically distributed roll-twist coupling reduces the magnitude of oscillations in J, seen in plots of J vs chain length, to the extent found exptl. [on SciFinder (R)]
BibTeX: @article{RefWorks:370, author = {Luke Czapla and David Swigon and Wilma K. Olson}, title = {Sequence-Dependent Effects in the Cyclization of Short DNA.}, journal = {Journal of Chemical Theory and Computation}, year = {2006}, volume = {2}, number = {3}, pages = {685-695}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 6; CODEN: JCTCCE} }
Erie, D. A., Breslauer, K. J. & Olson, W. K.	A Monte Carlo method for generating structures of short single-stranded DNA sequences. [Abstract] [BibTeX]	1993	Biopolymers	article
Abstract: A Monte Carlo method has been developed for generating the conformations of short single-stranded DNAs from arbitrary starting states. The chain conformers are constructed from energetically favorable arrangements of the constituent mononucleotides. Min. energy states of individual dinucleotide monophosphate mols. are identified using a torsion angle minimizer. The glycosyl and acyclic backbone torsions of the dimers are allowed to vary, while the sugar rings are held fixed in one of the two preferred puckered forms. A total of 108 conformationally distinct states per dimer are considered in this first stage of minimization. The torsion angles within 5 kcal/mol of the global min. in the resulting optimized states are then allowed to vary by +-10 Deg in an effort to est. the breadth of the different local min. The energies of a total of 2187 (37) angle combinations are examd. per local conformational min. Finally, the energies of all dinucleotide conformers are scaled so that the populations of differently puckered sugar rings in the theor. sample match those found in NMR soln. studies. This last step is necessitated by limitations in the theor. methods to predict DNA sugar puckering accurately. The conformer populations of the individual acyclic torsion angles in the composite dimer ensembles are found to be in good agreement with the distributions of backbone conformations deduced from NMR coupling consts. and the frequencies of glycosyl conformations in x-ray crystal structures, suggesting that the low energy states are reasonable. The low energy dimer forms (consisting of 150-325 conformational states per dimer step) are next used as variables in a Monte Carlo algorithm, which generates the conformations of single-stranded d(CXnG) chains, were X = A, T and n = 3, 4, 5. The oligonucleotides are built sequentially from the 5' end of the chain using random nos. to select the conformations of overlapping dimer units. The simulations are very fast, involving a total of 106 conformations per chain sequence. The potential errors in the buildup procedure are minimized by taking advantage of known rotational interdependences in the sugar-phosphate backbone. The distributions of oligonucleotide conformations are examd. in terms of the magnitudes, positions, and orientations of the end-to-end vectors of the chains. The differences in overall flexibility and extension of the oligomers are discussed in terms of the conformations of the constituent dinucleotide steps, while the general methodol. is discussed and compared with other nucleic acid model building techniques. [on SciFinder (R)]
BibTeX: @article{RefWorks:313, author = {Dorothy A. Erie and Kenneth J. Breslauer and Wilma K. Olson}, title = {A Monte Carlo method for generating structures of short single-stranded DNA sequences.}, journal = {Biopolymers}, year = {1993}, volume = {33}, number = {1}, pages = {75-105}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 6; CODEN: BIPMAA; CAS Registry Numbers: 1969-54-6; 4251-20-1; 4336-87-2; 4624-07-1; 4829-64-5; 23339-45-9; 75567-41-8; 75579-55-4; 77540-75-1; 92396-49-1; 144994-91-2; 144994-92-3 Role: PRP (Properties) (conformation of, Monte Carlo method for calcn. of)} }
Erie, D. A., Jones, R. A., Olson, W. K., Sinha, N. K. & Breslauer, K. J.	Melting behavior of a covalently closed, single-stranded, circular DNA. [Abstract] [BibTeX]	1989	Biochemistry	article
Abstract: A 26 residue deoxynucleotide sequence d(TTCCT5GGAATTCCT5GGAA), which folds intramolecularly to a dumbbell-shaped, double-hairpin structure with a gap between the 3' and the 5' ends, was synthesized. T4 polynucleotide kinase was used to phosphorylate the 5' end followed by T4 DNA ligase to close the 3' and 5' ends. Melting of the dumbbell structure formed by this ligated sequence produces a covalently closed, single-stranded, circular final state. Calorimetric and spectroscopic techniques were used to characterize thermodynamically the melting behavior of the ligated mol. and compared it with the corresponding melting behavior of its unligated precursor. This comparison enabled the characterization of the influence of single-stranded ring closure on intramol. duplex melting. The data reveal that ring closure produces a thermally more stable structure which exhibits significantly altered melting thermodn. These thermodn. differences are rationalized in terms of differential solvation and differential counterion assocn. between the ligated and unligated mols. The importance of such constrained dumbbell structures as models for hairpins, cruciforms, and locally melted domains with naturally occurring DNA polymers is also noted. [on SciFinder (R)]
BibTeX: @article{RefWorks:332, author = {Dorothy A. Erie and Roger A. Jones and Wilma K. Olson and Navin K. Sinha and Kenneth J. Breslauer}, title = {Melting behavior of a covalently closed, single-stranded, circular DNA.}, journal = {Biochemistry}, year = {1989}, volume = {28}, number = {1}, pages = {268-273}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BICHAW; CAS Registry Numbers: 117988-12-2 Role: BIOL (Biological study) (melting and phosphorylation of); 70755-49-6; 110743-49-2; 117982-68-0 Role: PROC (Process) (melting of); 117982-70-4P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and ligation and melting of); 117982-69-1P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and melting of, as model for closed circular single-stranded DNA)} }
Erie, D. A., Suri, A. K., Breslauer, K. J., Jones, R. A. & Olson, W. K.	Theoretical predictions of DNA hairpin loop conformations: correlations with thermodynamic and spectroscopic data. [Abstract] [BibTeX]	1993	Biochemistry	article
Abstract: A computational procedure for generating conformations of DNA hairpin loop structures from a broad range of low-energy starting states is described. The starting point of the modeling is the distribution of oligonucleotide chain conformations obtained from Monte Carlo simulations of feasible dinucleotide steps. Structures that meet the spatial criteria for hairpin loop formation are selected from the distributions and subsequently minimized using all-atom mol. mechanics. Both d(CTnG) and d(CAnG) oligomers, where n = 3, 4, or 5, are modeled. These sequences are chosen because of the large no. of published NMR and thermodn. studies on DNA hairpins contg. thymine or adenine residues. The minimized three-dimensional hairpin loop structures are compared with one another as well as analyzed in terms of available exptl. data. The computational approach provides the first detailed anal. of DNA hairpin loop structure in terms of a multistate conformational model. Investigation of the minimized conformations reveals several interesting structural features. First, hairpin loops of the same sequence adopt several distinctly different conformations, as opposed to minor variants of the same equil. structure, that could potentially interconvert in soln. Second, in contrast to double-helical nucleic acids, the hairpin loop models exhibit hydrophobic and hydrophilic surfaces. The different disposition of hydrophobic groups in loops vs. duplexes could modulate both protein-nucleic acid interactions and nucleic acid self-assocn. Third, perpendicular arom. interactions of loop residues are obsd. in many of the computed hairpins. This sort of interaction might be important in the stabilization of non-hydrogen-bonded nucleic acid secondary and tertiary structures. The predicted structural features in the models help, in addn., to account for the unusual thermodn. properties of DNA hairpin loops. Comparison of the theor.-generated NOEs in different structures further reveals that very different mol. structures and interaction can, in principle, produce the same NOEs. The multistate description suggested by this observation differs from the conventional interpretation of DNA soln. structure in terms of the fluctuations about a single preferred chain conformation. There is not necessarily only one set of closely related structures consistent with the obsd. data. [on SciFinder (R)]
BibTeX: @article{RefWorks:315, author = {Dorothy A. Erie and Asif K. Suri and Kenneth J. Breslauer and Roger A. Jones and Wilma K. Olson}, title = {Theoretical predictions of DNA hairpin loop conformations: correlations with thermodynamic and spectroscopic data.}, journal = {Biochemistry}, year = {1993}, volume = {32}, number = {2}, pages = {436-454}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 6; CODEN: BICHAW; CAS Registry Numbers: 75567-41-8; 75579-55-4; 77540-75-1; 92396-49-1; 144994-91-2; 144994-92-3 Role: PRP (Properties) (hairpin loop conformation of, theor. prediction of, thermodn. and spectrometry in relation to); 111853-74-8; 111853-75-9; 117988-81-5; 117988-84-8; 118025-39-1; 129874-43-7; 129874-45-9 Role: PRP (Properties) (hairpin loop conformation of, thermodn. of)} }
Fenley, M. O., Manning, G. S., Marky, N. L. & Olson, W. K.	Excess counterion binding and ionic stability of kinked and branched DNA. [Abstract] [BibTeX]	1998	Biophysical chemistry	article
Abstract: The excess no. of counterions assocd. with kinked and branched DNA and the ionic stabilities of these structures as a function of chain length and both Na+ and Mg2+ salt concn., using numerical counterion condensation theory, are computed. The DNA structures are modeled as 2 or more finite lines of phosphate charges radiating from the kink or junction center. The no. of excess counterions around the (40-90 Deg) kinked duplex is very small (at most four). The geometries of large 3- and 4-way DNA junctions (with >50 base pairs per arm) in solns. contg. low to moderate NaCl concns., by contrast, accumulate a substantial no. of excess Na+ (>20) but ?15 Mg2+ counterions. The excess no. of counterions surrounding the kinked linear chain and the branched DNA structures either remains invariant or increases with chain length, tending to reach a plateau value. Open configurations, such as the planar Y-shaped 3-way junction (with 3 120 Deg inter-arm angles) and the 90 Deg cross-shaped four-way junction, are ionically more stable than compact geometries, such as pyramidal 3-way junctions and X-shaped 4-way junctions, over the entire range of salt concn. considered (10-5-10-1 M NaCl or MgCl2). The ionic stabilities of the compact forms increase with increasing salt concn. and become comparable to those of the extended geometries at high salt (esp. when Mg2+ is the supporting salt). [on SciFinder (R)]
BibTeX: @article{RefWorks:400, author = {Marcia O. Fenley and Gerald S. Manning and Nancy L. Marky and Wilma K. Olson}, title = {Excess counterion binding and ionic stability of kinked and branched DNA.}, journal = {Biophysical chemistry}, year = {1998}, volume = {74}, number = {2}, pages = {135-152}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BICIAZ; CAS Registry Numbers: 7439-95-4 (Magnesium); 7440-23-5 (Sodium) Role: BAC (Biological activity or effector, except adverse), BSU (Biological study, unclassified), BIOL (Biological study) (excess counterion binding and ionic stability of kinked and branched DNA)} }
Fenley, M. O., Manning, G. S. & Olson, W. K.	Electrostatic persistence length of a smoothly bending polyion computed by numerical counterion condensation theory. [Abstract] [BibTeX]	1992	Journal of Physical Chemistry	article
Abstract: Using numerical counterion condensation theory, the electrostatic component of the persistence length of DNA is computed for three models. In the line model, the phosphate charges are represented as points uniformly distributed on a line of zero radius. In the helical model, the phosphates are given the three-dimensional coordinates deduced from x-ray fiber diffraction; the helical model is considered with and without the dielec. satn. effect. For each model, the free energy of bending smoothly to a specified radius of curvature is calcd. All models exhibit strong end effects for finite-length DNA. The most reliable model is the helical model with dielec. satn. Persistence lengths calcd. for it are linearly correlated, to good numerical approxn., with the inverse concn. of salt. Comparison with exptl. data suggests that real thermal bending fluctuations of DNA in soln. may not be describable as the smooth length-invariant bending postulated by any of the models. [on SciFinder (R)]
BibTeX: @article{RefWorks:320, author = {Marcia O. Fenley and Gerald S. Manning and Wilma K. Olson}, title = {Electrostatic persistence length of a smoothly bending polyion computed by numerical counterion condensation theory.}, journal = {Journal of Physical Chemistry}, year = {1992}, volume = {96}, number = {10}, pages = {3963-3969}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CA Section Cross-references: 9, 68; CODEN: JPCHAX} }
Fenley, M. O., Manning, G. S. & Olson, W. K.	A numerical counterion condensation analysis of the B-Z transition of DNA. [Abstract] [BibTeX]	1990	Biopolymers	article
Abstract: The salt dependence of the B-Z transition in DNA was examd. by means of the counterion condensation theory adapted to structurally realistic coordinates of the phosphate groups. The ionic contribution to the free energy difference DG is computed for both the ZI and ZII conformations over broad ranges of NaCl and MgCl2 concns. and polymer lengths. For the solvent both a const.-dielec. model (dielec. const. set to 78.3) and a dielec. satn. model (distance-dependent const.) were employed. Where comparison can be made, the results for the const.-dielec. model are similar to those obtained by other workers for the same model but with different computational methods. The existence of a low-salt transition, and its location when it does occur, depends strongly on the DNA length and on the dielec. model. The behavior of ZI and ZII are qual. similar throughout the entire salt range for the const.-dielec. model, but qual. different if dielec. satn. is simulated, as is necessary for a realistic description. The ionic DG, in the presence of dielec. satn., bears comparison with the high-salt trend of the measured total DG if Z-DNA is predominantly ZI, but not if it is predominantly ZII. [on SciFinder (R)]
BibTeX: @article{RefWorks:325, author = {Marcia O. Fenley and Gerald S. Manning and Wilma K. Olson}, title = {A numerical counterion condensation analysis of the B-Z transition of DNA.}, journal = {Biopolymers}, year = {1990}, volume = {30}, number = {13-14}, pages = {1205-1213}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BIPMAA; CAS Registry Numbers: 7439-95-4 (Magnesium); 7440-23-5 (Sodium) Role: BIOL (Biological study) (DNA binding of, ionic strength effect on, in counterion condensation study)} }
Fenley, M. O., Manning, G. S. & Olson, W. K.	Approach to the limit of counterion condensation. [Abstract] [BibTeX]	1990	Biopolymers	article
Abstract: According to counterion condensation theory, one of the contributions to the polyelectrolyte free energy is a pairwise sum of Debye-Hueckel potentials between polymer charges that are reduced by condensed counterions. When the polyion model is taken as an infinitely long and uniformly spaced line of charges, a simple closed expression for the summation, combined with entropy-derived mixing contributions, leads to the central result of the theory, a condensed fraction of counterions dependent only on the linear charge d. of the polyion and the valence of the counterion, stable against increases of salt up to concns. in excess of 0.1M. Here the sum is numerically evaluated for B-DNA models other than the infinite line of B-DNA charges. For a finite-length line there are end effects at low salt. The condensation limit is reached as a flat plateau by increasing the salt concn. At a fixed salt concn. the condensation limit is reached by increasing the length of the line. At moderate salt even very short B-DNA line-model oligomers have condensed fractions not far from the infinite polymer limit. For a long double-helical array with charge coordinates at the phosphates of B-DNA, the limiting condensed fraction appears to be approached at low salt. In contrast to the results for the line of charges, however, the computed condensed fraction varies strongly with salt in the range of exptl. typical concns. Salt invariance is restored, in agreement with both the line model and exptl. data, when dielec. satn. is considered by means of a distance-dependent dielec. function. For sufficiently long B-DNA line and helical models, at typical salt concns., the counterion binding fraction approaches the polymer limit as a linear function of 1/P, where P is the no. of phosphate groups of B-DNA. [on SciFinder (R)]
BibTeX: @article{RefWorks:326, author = {Marcia O. Fenley and Gerald S. Manning and Wilma K. Olson}, title = {Approach to the limit of counterion condensation.}, journal = {Biopolymers}, year = {1990}, volume = {30}, number = {13-14}, pages = {1191-1203}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BIPMAA; CAS Registry Numbers: 7439-95-4 (Magnesium); 7440-23-5 (Sodium) Role: PRP (Properties) (condensation limit of, with B DNA model oligomers, ionic strength effect on)} }
Fenley, M. O., Olson, W. K., Chua, K. & Boschitsch, A. H.	Fast adaptive multipole method for computation of electrostatic energy in simulations of polyelectrolyte DNA. [Abstract] [BibTeX]	1996	Journal of Computational Chemistry	article
Abstract: This article presents a fast adaptive method for the computation of long-range electrostatic interactions in computer simulations of polyelectrolyte DNA. Classically, the computation of electrostatic energy involves a direct summation of all pairwise interactions due to the charges phosphate groups in the mol. This results in an N-body interaction problem with an asymptotic time complexity of O(N2) which is computationally very expensive and limits the no. of phosphate groups that can be used in computer simulations of polyelectrolyte DNA to at most several hundred. We describe an effort to speed up computer simulations of polyelectrolyte DNA with the use of a fast adaptive hierarchical algorithm for the computation of electrostatic energy (i.e., modified Debye-Huckel energy). The asymptotic time complexity is reduced to O(N) with the implementation of the fast hierarchical algorithm on serial computers. This is achieved by grouping phosphate groups into an adaptive hierarchical data structure and computing the interactions between groups using low order multipole and Taylor series expansions expressed in Cartesian coordinates. We first examine the accuracy and speed enhancements of the fast hierarchical method in the computation of the electrostatic energy of circular DNA at zero and high salt concns. The fast hierarchical method is further tested in a one-step Monte Carlo (MC) simulated annealing algorithm for closed circular supercoiled DNA. In all cases, we observe order of magnitude redns. in the computation time with negligible loss of numerical accuracy in the electrostatic energy computation. [on SciFinder (R)]
BibTeX: @article{RefWorks:413, author = {Marcia O. Fenley and Wilma K. Olson and Kiat Chua and Alexander H. Boschitsch}, title = {Fast adaptive multipole method for computation of electrostatic energy in simulations of polyelectrolyte DNA.}, journal = {Journal of Computational Chemistry}, year = {1996}, volume = {17}, number = {8}, pages = {976-991}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: JCCHDD} }
Fenley, M. O., Olson, W. K. & Manning, G. S.	Dependence of Counterion Binding on DNA Shape as Determined By Counterion Condensation Theory. [Abstract] [BibTeX]	2000	Macromolecules	article
Abstract: We have computed the fraction of DNA phosphate charge neutralized by condensed counterions for parallel pairs of linear DNA segments, DNA circles, and representative closed-circular supercoiled DNA configurations ranging in length from 42 to 3000 base pairs. We find significant but small uptake of condensed counterions for the more compact structures relative to an isolated linear DNA segment. [on SciFinder (R)]
BibTeX: @article{RefWorks:388, author = {Marcia O. Fenley and Wilma K. Olson and Gerald S. Manning}, title = {Dependence of Counterion Binding on DNA Shape as Determined By Counterion Condensation Theory.}, journal = {Macromolecules}, year = {2000}, volume = {33}, number = {5}, pages = {1899-1903}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: MAMOBX; CAS Registry Numbers: 7440-23-5 (Sodium) Role: BPR (Biological process), BSU (Biological study, unclassified), BIOL (Biological study), PROC (Process) (dependence of counterion binding on DNA shape as detd. by counterion condensation theory)} }
Fenley, M. O., Olson, W. K., Tobias, I. & Manning, G. S.	Electrostatic effects in short superhelical DNA. [Abstract] [BibTeX]	1994	Biophysical chemistry	article
Abstract: The authors present Monte Carlo simulations of the equil. configurations of short closed circular DNA that obeys a combined elastic, hard-sphere, and electrostatic energy potential. The authors employ a B-spline representation to model chain configuration and simulate the effects of salt on chain folding by varying the Debye screening parameter. The authors obtain global equil. configurations of closed circular DNA, with several imposed linking no. differences, at two salt concns. (specifically at the extremes of no added salt and the high salt regime), and for different chain lengths. Minimization of the composite elastic/long-range potential energy under the constraints of ring closure and fixed chain length is found to produce structures that are consistent with the configurations of short supercoiled DNA obsd. exptl. The structures generated under the constraints of an electrostatic potential are less compact than those subjected only to an elastic term and a hard-sphere constraint. For a fixed linking no. difference greater than a crit. value, the interwound structures obtained under the condition of high salt are more compact than those obtained under the condition of no added salt. In the case of no added salt, the electrostatic energy plays a dominant role over the elastic energy in dictating the shape of the closed circular DNA. The DNA supercoil opens up with increasing chain length at low salt concn. A branched three-leaf rose structure with a fixed linking no. difference is higher in energy than the interwound form at both salt concns. employed here. [on SciFinder (R)]
BibTeX: @article{RefWorks:427, author = {Marcia O. Fenley and Wilma K. Olson and Irwin Tobias and Gerald S. Manning}, title = {Electrostatic effects in short superhelical DNA.}, journal = {Biophysical chemistry}, year = {1994}, volume = {50}, number = {3}, pages = {255-271}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BICIAZ} }
Ge, W., Schneider, B. & Olson, W. K.	Knowledge-based elastic potentials for docking drugs or proteins with nucleic acids. [Abstract] [BibTeX]	2005	Biophysical journal	article
Abstract: Elastic ellipsoidal functions defined by the obsd. hydration patterns around the DNA bases provide a new basis for measuring the recognition of ligands in the grooves of double-helical structures. Here a set of knowledge-based potentials suitable for quant. description of such behavior is extd. from the obsd. positions of water mols. and amino acid atoms that form hydrogen bonds with the nitrogenous bases in high resoln. crystal structures. Energies based on the displacement of hydrogen-bonding sites on drugs in DNA-crystal complexes relative to the preferred locations of water binding around the heterocyclic bases are low, pointing to the reliability of the potentials and the apparent displacement of water mols. by drug atoms in these structures. The validity of the energy functions has been further examd. in a series of sequence substitution studies based on the structures of DNA bound to polyamides that have been designed to recognize the minor-groove edges of Watson-Crick base pairs. The higher energies of binding to incorrect sequences superimposed (without conformational adjustment or displacement of polyamide ligands) on obsd. high resoln. structures confirm the hypothesis that the drug subunits assoc. with specific DNA bases. The knowledge-based functions also account satisfactorily for the measured free energies of DNA-polyamide assocn. in soln. and the obsd. sites of polyamide binding on nucleosomal DNA. The computations are generally consistent with mechanisms by which minor-groove binding ligands are thought to recognize DNA base pairs. The calcns. suggest that the asym. distributions of hydrogen-bond-forming atoms on the minor-groove edge of the base pairs may underlie ligand discrimination of G.C from C.G pairs, in addn. to the commonly believed role of steric hindrance. The anal. of polyamide-bound nucleosomal structures reveals other discrepancies in the expected chem. design, including unexpected contacts to DNA and modified base pair targets of some ligands. The ellipsoidal potentials thus appear promising as a math. tool for the study of drug- and protein-DNA interactions and for gaining new insights into DNA-binding mechanisms. [on SciFinder (R)]
BibTeX: @article{RefWorks:371, author = {Wei Ge and Bohdan Schneider and Wilma K. Olson}, title = {Knowledge-based elastic potentials for docking drugs or proteins with nucleic acids.}, journal = {Biophysical journal}, year = {2005}, volume = {88}, number = {2}, pages = {1166-1190}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-7; CODEN: BIOJAU; CAS Registry Numbers: 65-71-4 (Thymine) Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PYP (Physical process), BIOL (Biological study), PROC (Process) (base pair with adenine; knowledge-based elastic potentials for docking polyamide drugs or proteins with nucleic acid base pairs in relation to hydration patterns and hydrogen bonding properties); 73-40-5 (Guanine) Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PYP (Physical process), BIOL (Biological study), PROC (Process) (base pair with cytosine; knowledge-based elastic potentials for docking polyamide drugs or proteins with nucleic acid base pairs in relation to hydration patterns and hydrogen bonding properties); 71-30-7 (Cytosine) Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PYP (Physical process), BIOL (Biological study), PROC (Process) (base pair with guanine; knowledge-based elastic potentials for docking polyamide drugs or proteins with nucleic acid base pairs in relation to hydration patterns and hydrogen bonding properties); 73-24-5 (Adenine) Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PYP (Physical process), BIOL (Biological study), PROC (Process) (base pair with thymine; knowledge-based elastic potentials for docking polyamide drugs or proteins with nucleic acid base pairs in relation to hydration patterns and hydrogen bonding properties); 7732-18-5 (Water); 147859-82-3; 181028-22-8; 181028-25-1 Role: BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PYP (Physical process), BIOL (Biological study), PROC (Process) (knowledge-based elastic potentials for docking polyamide drugs or proteins with nucleic acid base pairs in relation to hydration patterns and hydrogen bonding properties)} }
Gelbin, A., Schneider, B., Clowney, L., Hsieh, S., Olson, W. K. & Berman, H. M.	Geometric Parameters in Nucleic Acids: Sugar and Phosphate Constituents. [Abstract] [BibTeX]	1996	Journal of the American Chemical Society	article
Abstract: A statistical survey of the torsion angles, bond angles, and bond lengths in the sugar and phosphate groups of well-refined mononucleoside, mononucleotide, dinucleoside monophosphate, and trinucleoside diphosphate crystal structures contained in the Cambridge Structural Database and the Nucleic Acid Database is reported. The mean values of the geometrical parameters in these structures and their estd. std. deviations are sepd. according to their chem. and conformation. These new parameters serve as a basis for a dictionary of std. nucleic acid geometry. [on SciFinder (R)]
BibTeX: @article{RefWorks:416, author = {Anke Gelbin and Bohdan Schneider and Lester Clowney and Shu-Hsin Hsieh and Wilma K. Olson and Helen M. Berman}, title = {Geometric Parameters in Nucleic Acids: Sugar and Phosphate Constituents.}, journal = {Journal of the American Chemical Society}, year = {1996}, volume = {118}, number = {3}, pages = {519-529}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 33-9; CA Section Cross-references: 75; CODEN: JACSAT} }
Goldman, C. & Olson, W. K.	DNA denaturation as a problem of translational-symmetry restoration. [Abstract] [BibTeX]	1993	Physical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics	article
Abstract: The authors study the quantum-mech. version of a model proposed by Peyrard and Bishop [Phys. Rev. Lett.62, 2755 (1989)] to describe the denaturation phenomenon on the DNA double helix. The authors characterize denaturation as a phase transition leading to the restoration of the translational invariance of the system. The problem is approached via a modified perturbative theory which incorporates also nonperturbative effects. These are accounted by an auxiliary random variable (u) describing the equil. positions of the constituting particles. The criticality of the model is revealed by analyzing equations involving the first and second cumulants of the u-distribution function. As a consequence, an anal. expression for the crit. temp. Tc is obtained as a function of all model parameters. [on SciFinder (R)]
BibTeX: @article{RefWorks:310, author = {Carla Goldman and Wilma K. Olson}, title = {DNA denaturation as a problem of translational-symmetry restoration.}, journal = {Physical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics}, year = {1993}, volume = {48}, number = {2}, pages = {1461-1468}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: PLEEE8} }
Gorin, A. A., Zhurkin, V. B. & Olson, W. K.	B-DNA twisting correlates with base-pair morphology. [Abstract] [BibTeX]	1995	Journal of Molecular Biology	article
Abstract: The obsd. sequence dependence of the mean twist angles in 38 B-DNA crystal structures can be understood in terms of simple geometrical features of the constituent base-pairs. Structures with low twist appear to unwind in response to severe steric clashes of large exocyclic groups (such as NH2-NH2) in the major and minor grooves, while those with high twist are subjected to lesser contacts (H-O and H-H). The authors offer a simple clash function that depends on base-pair morphol. (i.e. the chem. constitution of base-pairs) and satisfactorily accounts for the twist angles of the ten common Watson-Crick dimer steps both in the solid state and in soln. The twist-clash correlation that the authors find here still holds when extended to modified bases. In addn. to Calladine's purine-purine clashes, the authors add other close contacts between bases in the grooves, and consider the conformational restrictions on the geometry of the sugar-phosphate backbone (namely, the authors emphasize the tendency of DNA to conserve virtual backbone length). The significance of this finding is threefold: (1) sequence-dependent DNA twisting is directly involved with protein-DNA interactions; (2) strong correlation between Twist and Roll helps to elucidate the bending of the double helix as a function of base sequence; (3) it is possible to anticipate the effects of chem. modifications on twisting and bending. The mutual correlations of other structural parameters with the twist make this angle a primary determinant of DNA conformational heterogeneity. [on SciFinder (R)]
BibTeX: @article{RefWorks:423, author = {Andrey A. Gorin and Victor B. Zhurkin and Wilma K. Olson}, title = {B-DNA twisting correlates with base-pair morphology.}, journal = {Journal of Molecular Biology}, year = {1995}, volume = {247}, number = {1}, pages = {34-48}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: JMOBAK} }
Hao, M. H. & Olson, W. K.	Molecular modeling and energy refinement of supercoiled DNA. [Abstract] [BibTeX]	1989	Journal of Biomolecular Structure & Dynamics	article
Abstract: A method is presented for constructing the complete at. structure of supercoiled DNA starting from a linear description of the double-helical pathway. The folding pathway is defined by piecewise B-spline curves and the atoms are initially positioned with respect to the local Frenet trihedra detd. by the equations of the curves. The resulting chem. structure is cor. and refined with an energy minimization procedure based on std. potential expressions. The refined mol. structure is then used to study the effects of supercoiling on the local secondary structure of DNA. The minimized structure is found to differ from an isotropic elastic rod model of the double helix, with the base pairs bending in an asym. fashion along the supercoiled trajectory. The starting trajectory is chosen so that the refined supercoiled structure is either underwound (10.37 base pairs per turn) or overwound (9.65 base pairs per turn) compared to the std. ten-fold B-DNA fiber diffraction model. The underwound supercoil is also lower in energy than the overwound duplex. The variation of base pair sequence in poly(dA).poly(dT), poly(dAT).poly(dTA), and poly(dA5T5).poly(dT5A5) is addnl. found to influence the secondary structural features along a given supercoiled pathway. Finally, the detailed features of the refined structures are found to be in agreement with known x-ray crystallog. structures of DNA oligomers. [on SciFinder (R)]
BibTeX: @article{RefWorks:327, author = {Ming Hong Hao and Wilma K. Olson}, title = {Molecular modeling and energy refinement of supercoiled DNA.}, journal = {Journal of Biomolecular Structure & Dynamics}, year = {1989}, volume = {7}, number = {3}, pages = {661-92, 1 plate}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CA Section Cross-references: 9; CODEN: JBSDD6; CAS Registry Numbers: 26966-61-0; 114939-93-4 Role: BIOL (Biological study) (double-stranded, supercoiling of, sequence dependence of); 27156-07-6 Role: BIOL (Biological study) (supercoiling of, sequence dependence of)} }
Hao, M. H. & Olson, W. K.	The global equilibrium configurations of supercoiled DNA. [Abstract] [BibTeX]	1989	Macromolecules	article
Abstract: The equil. configurations of circular DNA with imposed linking no. differences are studied by computer simulation. The configurational energy of the double helix is described by an isotropic elastic deformation model together with a pairwise potential for calcg. the self-interaction between distant points along the chain. The axis of the closed double-helical trajectory of the polymer is represented by piecewise cyclic B-spline curves that are approximated by a finite no. of controlling points. The global min. of the total potential energy is obtained with an algorithm that combines Metropolis-Monte Carlo sampling with a simulated annealing procedure. Simulation conditions are examd. as are the effects of adjustable energy parameters. The dependence of the algorithm on temp. is related to the actual chain length of the DNA through the well-known relationship between persistence length and temp. The predicted 3-dimensional arrangements are consistent with the configurations of supercoiled DNA obsd. in electron micrographs. The most stable structures of the closed chain are interwound configurations that are also critically dependent on the specified linking no. difference. The toroidal configuration is unstable and, upon energy minimization, is transformed to an interwound form. The optimized trajectories of knotted structures, however, are independent of the linking difference over the range of values examd. [on SciFinder (R)]
BibTeX: @article{RefWorks:329, author = {Ming Hong Hao and Wilma K. Olson}, title = {The global equilibrium configurations of supercoiled DNA.}, journal = {Macromolecules}, year = {1989}, volume = {22}, number = {8}, pages = {3292-3303}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CA Section Cross-references: 9; CODEN: MAMOBX} }
Hao, M. H. & Olson, W. K.	Modeling DNA supercoils and knots with B-spline functions. [Abstract] [BibTeX]	1989	Biopolymers	article
Abstract: A method is offered to model the complex trajectories of closed circular DNA supercoils and knots. The trajectories are approximated by polygons and anal. expressions of the curves are generated from the polygons with B-spline functions. The resulting curves are used to evaluate the writhe and elastic energy of a series of interrelated supercoils, and to generate detailed at. models of the deformed double helix. [on SciFinder (R)]
BibTeX: @article{RefWorks:330, author = {Ming Hong Hao and Wilma K. Olson}, title = {Modeling DNA supercoils and knots with B-spline functions.}, journal = {Biopolymers}, year = {1989}, volume = {28}, number = {4}, pages = {873-900}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-15; CA Section Cross-references: 6; CODEN: BIPMAA} }
Hingerty, B. E., Broyde, S. B. & Olson, W. K.	The poly(rU) coil: a minimum-energy model that matches experimental observations. [Abstract] [BibTeX]	1982	Biopolymers	article
Abstract: A model of the randomly coiling form of poly(U) based on min.-energy conformers of UpU is described. The blend of conformers is chosen to fit the C-C rotational populations derived in NMR studies of UpU and poly(U) and to match the exptl. unperturbed dimensions of the poly(U) chain. In addn., ests. of loop closure based on the model are comparable to the sizes of loops most frequently seen in model oligonucleotides. Approx. 60% of the conformers constituting the model are characterized by stacked, extended C2'-endo w'wy = tg-g+ rotations. The remainder of the chain is described by equal nos. of C3'-endo A (w'wy = g-g-g+) and Watson-Crick (w'wy = g-tt) helical arrangements. [on SciFinder (R)]
BibTeX: @article{RefWorks:347, author = {Brian E. Hingerty and Suse B. Broyde and Wilma K. Olson}, title = {The poly(rU) coil: a minimum-energy model that matches experimental observations.}, journal = {Biopolymers}, year = {1982}, volume = {21}, number = {6}, pages = {1167-1188}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BIPMAA; CAS Registry Numbers: 27416-86-0 Role: PRP (Properties) (conformation of, UpU min. energy conformers in study of); 2415-43-2 Role: PRP (Properties) (min. energy conformation of, poly(U) coil in relation to)} }
Jin, E., Katritch, V., Olson, W. K., Kharatisvili, M., Abagyan, R. & Pilch, D. S.	Aminoglycoside Binding in the Major Groove of Duplex RNA: The Thermodynamic and Electrostatic Forces that Govern Recognition. [Abstract] [BibTeX]	2000	Journal of Molecular Biology	article
Abstract: We use a combination of spectroscopic, calorimetric, viscometric and computer modeling techniques to characterize the binding of the aminoglycoside antibiotic, tobramycin, to the polymeric RNA duplex, poly(rI).poly(rC), which exhibits the characteristic A-type conformation that is conserved among natural and synthetic double-helical RNA sequences. Our results reveal the following significant features: (i) CD-detected binding of tobramycin to poly(rI).poly(rC) reveals an apparent site size of four base-pairs per bound drug mol.; (ii) tobramycin binding enhances the thermal stability of the host poly(rI).poly(rC) duplex, the extent of which decreases upon increasing in Na+ concn. and/or pH conditions; (iii) the enthalpy of tobramycin- poly(rI).poly(rC) complexation increases with increasing pH conditions, an observation consistent with binding-induced protonation of one or more drug amino groups; (iv) the affinity of tobramycin for poly(rI).poly(rC) is sensitive to both pH and Na+ concn., with increases in pH and/or Na+ concn. resulting in a concomitant redn. in binding affinity. The salt dependence of the tobramycin binding affinity reveals that the drug binds to the host RNA duplex as trication. (v) The thermodn. driving force for tobramycin- poly(rI).poly(rC) complexation depends on pH conditions. Specifically, at pH?6.0, tobramycin binding is entropy driven, but is enthalpy driven at pH>6.0. (vi) Viscometric data reveal non-intercalative binding properties when tobramycin complexes with poly(rI).poly(rC), consistent with a major groove-directed mode of binding. These data also are consistent with a binding-induced redn. in the apparent mol. length of the host RNA duplex. (vii) Computer modeling studies reveal a tobramycin-poly(rI).poly(rC) complex in which the drug fits snugly at the base of the RNA major groove and is stabilized, at least in part, by an array of hydrogen bonding interactions with both base and backbone atoms of the host RNA. These studies also demonstrate an inability of tobramycin to form a stable low-energy complex with the minor groove of the poly(rI).poly(rC) duplex. In the aggregate, our results suggest that tobramycin-RNA recognition is dictated and controlled by a broad range of factors that include electrostatic interactions, hydrogen bonding interactions, drug protonation reactions, and binding-induced alterations in the structure of the host RNA. These modulatory effects on tobramycin-RNA complexation are discussed in terms of their potential importance for the selective recognition of specific RNA structural motifs, such as asym. internal loops or hairpin loop-stem junctions, by aminoglycoside antibiotics and their derivs. (c) 2000 Academic Press. [on SciFinder (R)]
BibTeX: @article{RefWorks:387, author = {Emily Jin and Vsevolod Katritch and Wilma K. Olson and Malkhaz Kharatisvili and Ruben Abagyan and Daniel S. Pilch}, title = {Aminoglycoside Binding in the Major Groove of Duplex RNA: The Thermodynamic and Electrostatic Forces that Govern Recognition.}, journal = {Journal of Molecular Biology}, year = {2000}, volume = {298}, number = {1}, pages = {95-110}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: JMOBAK} }
Jin, R., Jr., W. H. C., Srinivasan, A. R., Olson, W. K., Breslow, R. & Breslauer, K. J.	Comparative spectroscopic, calorimetric, and computational studies of nucleic acid complexes with 2',5versus 3',5phosphodiester linkages. [Abstract] [BibTeX]	1993	Proceedings of the National Academy of Sciences of the United States of America	article
Abstract: The authors have used a combination of spectroscopic, calorimetric, and computational techniques to characterize the properties of nucleic acid complexes with 2',5 and 3',5phosphodiester linkages. Specifically, the authors have compared the properties of complexes formed by the assocn. of 3',5single-stranded 16-mers of adenylic acid (A16) and thymidylic acid (T16) with the complexes formed by the corresponding single-stranded 16-mers with 2',5phosphodiester linkages (A16 and T16). The authors' results reveal the following differential features: (i) the 3',5strands form either a duplex or a triplex, depending on the sodium ion concn., whereas the 2',5strands form either a triplex or no complex at all; (ii) the 2',5and 3',5triplexes exhibit significantly different CD spectra, suggesting that the two triplex states are conformationally nonequivalent; (iii) the 2',5triplex has a lower charge d. than the 3',5triplex; (i.v.) the thermal stability of the 3',5triplex, as expected, is concn. dependent, whereas the thermal stability of the 2',5triplex is concn. independent; (v) relative to their component single strands, the 2',5triplex is thermodynamically much less stable than the 3',5triplex, despite being thermally more stable; (vi) the reduced thermodn. stability of the 2',5triplex relative to the 3',5triplex is overwhelmingly enthalpic in origin. In the aggregate, the authors' results reveal and characterize significant differences in the properties of complexes formed by the assocn. of strands with identical base sequences but different phosphodiester linkages. The authors describe a structural model that is consistent with many of the differential properties obsd. The authors also speculate on how these differential properties may have provided an evolutionary advantage for 3',5linkages and how the properties of 2',5complexes might be exploited in antisense strategies. [on SciFinder (R)]
BibTeX: @article{RefWorks:309, author = {Renzhe Jin and William H. Chapman Jr. and Annankoil R. Srinivasan and Wilma K. Olson and Ronald Breslow and Kenneth J. Breslauer}, title = {Comparative spectroscopic, calorimetric, and computational studies of nucleic acid complexes with 2',5\"-versus 3',5\"-phosphodiester linkages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {1993}, volume = {90}, number = {22}, pages = {10568-10572}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: PNASA6; CAS Registry Numbers: 7440-23-5 (Sodium) Role: BIOL (Biological study) ((2'->5')- and (3'->5')-linked DNA response to); 152790-23-3; 152890-96-5 Role: PRP (Properties) (structure and thermodn. stability of, sodium effect on, (2'->5')-linked oligodeoxyribonucleotide structure in relation to)} }
Katritch, V., Bustamante, C. & Olson, W. K.	Pulling Chromatin Fibers: Computer Simulations of Direct Physical Micromanipulations. [Abstract] [BibTeX]	2000	Journal of Molecular Biology	article
Abstract: A low-resoln. mol. model, which combines the known mech. properties of protein-free DNA with the accumulating picture of chromatosome structure, has been developed to account for the stretching of single chromatin fibers by an imposed external force. Force-extension characteristics of sets of chains accumulated by Monte Carlo sampling are consistent with recently obsd. findings in the non-destructive regime (<20 pN imposed force), where the structure of the chromatosome remains intact. The correspondence between simulation and the relaxation phase of the expt. limits the equil. entry-exit angle of linker DNA on the chromatosome to W=50(+-10) Deg and the effective DNA linker length to Leff=40(+-5) bp. The computed force-extension characteristics are relatively insensitive to other parameters of the model, precluding their accurate estn. The introduction of an attractive potential between closely spaced nucleosomes reproduces the added initial resistance of single fibers to extension at high salt conditions. The consideration of elastic linkers also improves the fitting of assorted classical measurements of unstressed chromatin structure in soln. The overall picture of chromatin that emerges is an irregular, fluctuating, three-dimensional, zig-zag structure with intact, mech. stable chromatosome units and deformable linkers. The modeled fiber undergoes large-scale configurational rearrangements without significant perturbation of the constituent chromatosome beads, collapsing into a highly condensed form in response to small (<2kT) inter-nucleosomal attractions. (c) 2000 Academic Press. [on SciFinder (R)]
BibTeX: @article{RefWorks:389, author = {Vsevolod Katritch and Carlos Bustamante and Wilma K. Olson}, title = {Pulling Chromatin Fibers: Computer Simulations of Direct Physical Micromanipulations.}, journal = {Journal of Molecular Biology}, year = {2000}, volume = {295}, number = {1}, pages = {29-40}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-3; CODEN: JMOBAK} }
Katritch, V., Olson, W. K., Pieranski, P., Dubochet, J. & Stasiak, A.	Properties of ideal composite knots. [Abstract] [BibTeX]	1997	Nature (London)	article
Abstract: The shortest tube of const. diam. that can form a given knot represents the 'ideal' form of the knot. Ideal knots provide an irreducible representation of the knot, and they have some intriguing math. and phys. features, including a direct correspondence with the time-averaged shapes of knotted DNA mols. in soln. Here we describe the properties of ideal forms of composite knots-knots obtained by the sequential tying of two or more independent knots (called factor knots) on the same string. We find that the writhe (related to the handedness of crossing points) of composite knots is the sum of that of the ideal forms of the factor knots. By comparing ideal composite knots with simulated configurations of knotted, thermally fluctuating DNA, we conclude that the additivity of writhe applies also to randomly distorted configurations of composite knots and their corresponding factor knots. We show that composite knots with several factor knots may possess distinct structural isomers that can be interconverted only by loosening the knot. [on SciFinder (R)]
BibTeX: @article{RefWorks:407, author = {Vsevolod Katritch and Wilma K. Olson and Piotr Pieranski and Jacques Dubochet and Andrzej Stasiak}, title = {Properties of ideal composite knots.}, journal = {Nature (London)}, year = {1997}, volume = {388}, number = {6638}, pages = {148-151}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: NATUAS} }
Katritch, V., Olson, W. K., Vologodskii, A., Dubochet, J. & Stasiak, A.	Tightness of random knotting. [Abstract] [BibTeX]	2000	Physical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics	article
Abstract: Long polymers in soln. frequently adopt knotted configurations. To understand the phys. properties of knotted polymers, it is important to find out whether the knots formed at thermodn. equil. are spread over the whole polymer chain or rather are localized as tight knots. We present here a method to analyze the knottedness of short linear portions of simulated random chains. Using this method, we observe that knot-detg. domains are usually very tight, so that, for example, the preferred size of the trefoil-detg. portions of knotted polymer chains corresponds to just seven freely jointed segments. [on SciFinder (R)]
BibTeX: @article{RefWorks:386, author = {Vsevolod Katritch and Wilma K. Olson and Alexander Vologodskii and Jacques Dubochet and Andrzej Stasiak}, title = {Tightness of random knotting.}, journal = {Physical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics}, year = {2000}, volume = {61}, number = {5-B}, pages = {5545-5549}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 36-7; CODEN: PLEEE8} }
Kosikov, K. M., Gorin, A. A., Lu, X., Olson, W. K. & Manning, G. S.	Bending of DNA by Asymmetric Charge Neutralization: All-Atom Energy Simulations. [Abstract] [BibTeX]	2002	Journal of the American Chemical Society	article
Abstract: DNA dodecamers of the alternating d(CG).d(CG) sequence with six phosphate groups either charge-neutralized or substituted by neutral methylphosphonates across the major or minor groove have been subjected to energy minimization to det. the conformational effect of the asym. elimination of phosphate charge. We report bending angles, directions of bending, and detailed structural characteristics such as groove widths and local base-pair parameters. Our principal results are that charge neutralization on one face of the DNA induces significant bending toward the neutralized face, in agreement with theor. predictions on a simplified model and exptl. data on a similar base-pair sequence, and that the DNA conformation averaged over all stereospecific methylphosphonate substitutions is nearly the same as the conformation produced by charge neutralization of the phosphates. Individual isomers, however, cover a wide range of structures, with the magnitude and direction of overall bending sensitive to the precise stereochem. pattern of neutralization. Our simulation does not explicitly contain counterions, and the results therefore suggest that counterions can influence DNA structure by neutralizing the phosphate charge. These data provide new hints into the mol. mechanisms which underlie the deformations of DNA structure induced by the binding of pos. charged proteins and other tightly assocd. cationic species. [on SciFinder (R)]
BibTeX: @article{RefWorks:380, author = {Konstantin M. Kosikov and Andrey A. Gorin and Xiang-Jun Lu and Wilma K. Olson and Gerald S. Manning}, title = {Bending of DNA by Asymmetric Charge Neutralization: All-Atom Energy Simulations.}, journal = {Journal of the American Chemical Society}, year = {2002}, volume = {124}, number = {17}, pages = {4838-4847}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: JACSAT; CAS Registry Numbers: 25512-84-9 (Poly (dCdG) Role: PRP (Properties) (double-stranded; all-atom energy simulations of bending of DNA by asym. charge neutralization); 993-13-5 (Methylphosphonic acid) Role: PRP (Properties) (in DNA; all-atom energy simulations of bending of DNA by asym. charge neutralization)} }
Kosikov, K. M., Gorin, A. A., Zhurkin, V. B. & Olson, W. K.	DNA Stretching and Compression: Large-scale Simulations of Double Helical Structures. [Abstract] [BibTeX]	1999	Journal of Molecular Biology	article
Abstract: Computer-simulated elongation and compression of A- and B-DNA structures beyond the range of thermal fluctuations provide new insights into high energy activated forms of DNA implicated in biochem. processes, such as recombination and transcription. All-atom potential energy studies of regular poly(dG).poly(dC) and poly(dA).poly(dT) double helixes, stretched from compressed states of 2.0 .ANG. per base-pair step to highly extended forms of 7.0 .ANG. per residue, uncover four different hyperfamilies of right-handed structures that differ in mutual base-pair orientation and sugar-phosphate backbone conformation. The optimized structures embrace all currently known right-handed forms of double-helical DNA identified in single crystals as well as non-canonical forms, such as the original Watson-Crick duplex with trans conformations about the P-O5' and C5'-C4' backbone bonds. The lowest energy min. correspond to canonical A- and B-form duplexes. The calcns. further reveal a no. of unusual helical conformations that are energetically disfavored under equil. conditions but become favored when DNA is highly stretched or compressed. The variation of potential energy vs. stretching provides a detailed picture of dramatic conformational changes that accompany the transitions between various families of double-helical forms. In particular, the interchanges between extended canonical and non-canonical states are reminiscent of the cooperative transitions identified by direct stretching expts. The large-scale, concerted changes in base-pair inclination, brought about by changes in backbone and glycosyl torsion angles, could easily give rise to the obsd. sharp increase in force required to stretch single DNA mols. more than 1.6-1.65 times their canonical extension. Our extended duplexes also help to tie together a no. of previously known structural features of the RecA-DNA complex and offer a self-consistent stereochem. model for the single-stranded/duplex DNA recognition brought in register by recombination proteins. The compression of model duplexes, by contrast, yields non-canonical structures resembling the deformed steps in crystal complexes of DNA with the TATA-box binding protein (TBP). The cryst. TBP-bound DNA steps follow the calcd. compression-elongation pattern of an unusual vertical duplex with base planes highly inclined with respect to the helical axis, exposed into the minor groove, and accordingly accessible for recognition. Significantly, the double helix can be stretched by a factor of two and compressed roughly in half before its computed internal energy rises sharply. The energy profiles show that DNA extension-compression is related not only to the variation of base-pair Rise but also to concerted changes of Twist, Roll, and Slide. We suggest that the high energy activated forms calcd. here are crit. for DNA processing, e.g. nucleo-protein recognition, DNA/RNA synthesis, and strand exchange. (c) 1999 Academic Press. [on SciFinder (R)]
BibTeX: @article{RefWorks:395, author = {Konstantin M. Kosikov and Andrey A. Gorin and Victor B. Zhurkin and Wilma K. Olson}, title = {DNA Stretching and Compression: Large-scale Simulations of Double Helical Structures.}, journal = {Journal of Molecular Biology}, year = {1999}, volume = {289}, number = {5}, pages = {1301-1326}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: JMOBAK; CAS Registry Numbers: 24939-09-1 (Poly(dA).poly(dT); 25512-84-9 (Poly(dG).poly(dC) Role: BPR (Biological process), BSU (Biological study, unclassified), PEP (Physical, engineering or chemical process), PRP (Properties), BIOL (Biological study), PROC (Process) (DNA stretching and compression: large-scale simulations of double helical structures)} }
Langowski, J., Olson, W. K., Pedersen, S. C., Tobias, I., Westcott, T. P. & Yang, Y.	DNA supercoiling, localized bending and thermal fluctuations. [Abstract] [BibTeX]	1996	Trends in biochemical sciences	article
Abstract: A review, with 19 refs. The authors report here DNA supercoiling, localized bending and thermal fluctuations. [on SciFinder (R)]
BibTeX: @article{RefWorks:415, author = {Joerg Langowski and Wilma K. Olson and Scott C. Pedersen and Irwin Tobias and Timothy P. Westcott and Yang Yang}, title = {DNA supercoiling, localized bending and thermal fluctuations.}, journal = {Trends in biochemical sciences}, year = {1996}, volume = {21}, number = {2}, pages = {50}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-0; CODEN: TBSCDB} }
Li, T., Bathory, E., LaVoie, E. J., Srinivasan, A. R., Olson, W. K., Sauers, R. R., Liu, L. F. & Pilch, D. S.	Human Topoisomerase I Poisoning by Protoberberines: Potential Roles for Both Drug-DNA and Drug-Enzyme Interactions. [Abstract] [BibTeX]	2000	Biochemistry	article
Abstract: Protoberberines represent a structural class of org. cations that induce topoisomerase I-mediated DNA cleavage, a behavior termed topoisomerase I poisoning. We have employed a broad range of biophys., biochem., and computer modeling techniques to characterize and cross-correlate the DNA-binding and topoisomerase poisoning properties of four protoberberine analogs that differ with respect to the substituents on their A- and/or D-rings. Our data reveal the following significant features: (i) The binding of the four protoberberines unwinds duplex DNA by approx. 11 Deg, an observation consistent with an intercalative mode of interaction. (ii) Enthalpically favorable interactions, such as stacking interactions between the intercalated ligand and the neighboring base pairs, provide 2,3-dimethoxy .mchgt. 3,4-dimethoxy. These differences in topoisomerase I poisoning activity may reflect the differing abilities of the analogs to interact with specific functionalities on the enzyme, thereby stabilizing the enzyme in its cleavable state. In the aggregate, our results are consistent with a mechanistic model in which both ligand-DNA and ligand-enzyme interactions are important for the poisoning of topoisomerase I by protoberberines, with the DNA-directed interactions involving ring D and the enzyme-directed interactions involving ring A. It is reasonable to suggest that the poisoning of topoisomerase I by a broad range of other naturally occurring and synthetic ligands may entail a similar mechanism. [on SciFinder (R)]
BibTeX: @article{RefWorks:385, author = {Tsai-Kun Li and Eleanor Bathory and Edmond J. LaVoie and A. R. Srinivasan and Wilma K. Olson and Ronald R. Sauers and Leroy F. Liu and Daniel S. Pilch}, title = {Human Topoisomerase I Poisoning by Protoberberines: Potential Roles for Both Drug-DNA and Drug-Enzyme Interactions.}, journal = {Biochemistry}, year = {2000}, volume = {39}, number = {24}, pages = {7107-7116}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 1-12; CODEN: BICHAW; CAS Registry Numbers: 3486-67-7 (Palmatine); 19716-66-6; 178818-97-8; 286000-57-5 Role: BAC (Biological activity or effector, except adverse), BSU (Biological study, unclassified), BIOL (Biological study) (human topoisomerase I poisoning by protoberberines and potential roles for both drug-DNA and drug-enzyme interactions); 143180-75-0 Role: BPR (Biological process), BSU (Biological study, unclassified), BIOL (Biological study), PROC (Process) (human topoisomerase I poisoning by protoberberines: potential roles for both drug-DNA and drug-enzyme interactions)} }
Liu, G., Geurts, A. M., Yae, K., Srinivasan, A. R., Fahrenkrug, S. C., Largaespada, D. A., Takeda, J., Horie, K., Olson, W. K. & Hackett, P. B.	Target-site preferences of Sleeping Beauty transposons. [Abstract] [BibTeX]	2005	Journal of Molecular Biology	article
Abstract: The Sleeping Beauty (SB) transposon is a Tc1/mariner family transposon that has applications in vertebrate animals for gene transfer, gene-tagging, and human gene therapy. This study analyzed the target-site preferences of the SB transposon. At the genomic level, integration of SB transposons with respect to genes (exons and introns) and intergenic regions appears fairly random but not on a micro-scale. Although there appears to be a consensus sequence around the vicinity of the target sites, the primary sequence is not the detg. factor for target selection. When integrations were examd. over a limited topog., the sites used most often for integration did not match the consensus sequence. Rather, a unique deformation inherent in the sequence may be a recognition signal for target selection. The deformation is characterized by an angling of the target site such that the axis around the insertion site is off-center, the rotation of the helix (twisting) is non-uniform and there is an increase in the distance between the central base-pairs. These observations offer several hypothetical insights into the transposition process. These observations suggest that particular deformations of the double helix predicted by the Vstep algorithm can distinguish TA sites that vary by about 16-fold in their preferences for accommodating insertions of SB transposons. [on SciFinder (R)]
BibTeX: @article{RefWorks:372, author = {Geyi Liu and Aron M. Geurts and Kojiro Yae and A. R. Srinivasan and Scott C. Fahrenkrug and David A. Largaespada and Junji Takeda and Kyoji Horie and Wilma K. Olson and Perry B. Hackett}, title = {Target-site preferences of Sleeping Beauty transposons.}, journal = {Journal of Molecular Biology}, year = {2005}, volume = {346}, number = {1}, pages = {161-173}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 3-4; CA Section Cross-references: 13; CODEN: JMOBAK} }
Liu, G. & Olson, W. K.	Application of Fourier methods to computer simulation of supercoiled DNA. [Abstract] [BibTeX]	1995	Computational Polymer Science	article
Abstract: Fourier methods have been applied to model the overall geometry of a supercoiled DNA curve, the starting coordinates of which can be obtained from electron microscopy measurements or other theor. simulations. Evenly spaced points on a known DNA curve are selected and subsequently used to model the original curve in terms of a finite Fourier series. Hence, a simple anal. curve expression, which closely resembles the initial data, is obtained for anal. and optimization. Energy minimization of DNA supercoils represented by such finite Fourier series has been performed using an elastic energy model. Minimized configurations are identified for interwound supercoils of 1000 bp at various values of the linking no. difference, DLk. The configurational profiles of writhing nos. (Wr) and energy vs. DLk are similar to those of optimized structures previously found with a B-spline representation of the DNS supercoil. However, there are some notable differences that probably result from the more global nature of the Fourier modeling compared to the B-spline. At the same DLk, a higher value of the writhing no. and a lower energy of writhing no. and a lower energy are consistently obtained with the finite Fourier series representation. Unlike the B-spline minimized structures and the configurations identified earlier by finite element anal., only two families of supercoiled families, the figure-eight and the loose interwound forms at low DLK, are found to overlap; there is no overlapping of interwound configurational families at higher DLk. The optimized configurations of three-lobed 1000 bp branched DNA supercoils have also been identified. Different families of structures are found over a DLk range between -0.6 and 6.0. Family I, with three lobes of similar shape and size and with Wr ~ 0, occurs at low DLk values. Families II-VI also with three lobes of similar shape and size, exist over a range of DLK from 1.0 to 4.6. The structures in families IIa-Va with one lobe larger than the others have similar Wr values at the same DLk but are slightly higher in energy. Families VII and ViII of min. found between DLk of 3.2 and 6.0 are characterized by one interwound and two open lobes, the latter being similar to but smaller than the lobes in the simpler branched structures of families II-VI. The occurrence of branched interwound energy min. is consistent with the highly branched configurations of supercoiled DNA obsd. under the electron microscope. Configurational snapshots of long partially relaxed DNA plasmids (6400 bp) taken from electron microscopic images are found to optimize to closely related linear and branched interwound forms with writhing nos. comparable to those of the nearly planar projected starting states. The energy minimization tends to straighten and maximize nonbonded contacts between interwound double helical strands and to fix the size of the hairpin loops emerging from the interwound domains. The configurational similarities of these minimized andomstarting states with the families of optimized configurations systematically identified at shorter chain lengths affirm the completeness of the search of energy min. [on SciFinder (R)]
BibTeX: @article{RefWorks:421, author = {Guohua Liu and Wilma K. Olson}, title = {Application of Fourier methods to computer simulation of supercoiled DNA.}, journal = {Computational Polymer Science}, year = {1995}, volume = {5}, number = {1&2}, pages = {7-27}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-16; CA Section Cross-references: 6; CODEN: CPOSEJ} }
Liu, G., Schlick, T., Olson, A. J. & Olson, W. K.	Configurational transitions in Fourier series-represented DNA supercoils. [Abstract] [BibTeX]	1997	Biophysical journal	article
Abstract: A new Fourier series representation of supercoiled DNA is employed in Langevin dynamics simulations to study large-scale configurational motions of intermediate-length chains. The polymer is modeled as an ideal elastic rod subject to long-range van der Waals' interactions. The van der Waals' term prevents the self-contact of distant chain segments and also mimics attractive forces thought to stabilize the assocn. of closely spaced charged rods. The finite Fourier series-derived polymer formulation is an alternative to the piecewise B-spline curves used in past work to describe the motion of smoothly deformed supercoiled DNA in terms of a limited no. of independent variables. This study focuses on two large-scale configurational events: the interconversion between circular and figure-8 forms at a relatively low level of supercoiling, and the transformation between branched and interwound structures at a higher superhelical d. [on SciFinder (R)]
BibTeX: @article{RefWorks:404, author = {Guohua Liu and Tamar Schlick and Andrew J. Olson and Wilma K. Olson}, title = {Configurational transitions in Fourier series-represented DNA supercoils.}, journal = {Biophysical journal}, year = {1997}, volume = {73}, number = {4}, pages = {1742-1762}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 6-2; CODEN: BIOJAU} }
Lu, X., Babcock, M. S. & Olson, W. K.	Overview of nucleic acid analysis programs. [Abstract] [BibTeX]	1999	Journal of Biomolecular Structure & Dynamics	article
Abstract: A review with 42 refs. We outline the math. distinctions among seven of the most popular computer programs currently used to analyze the spatial arrangements of bases and base pairs in nucleic acid helical structures. The schemes fall into three basic categories on the basis of their definitions of rotational parameters: matrix-based, projection-based, and combined matrix- and projection-based. The approaches also define and construct base and base-pair coordinate frames in a variety of ways. Despite these math. distinctions, the computed parameters from some programs are strongly correlated and directly comparable. By contrast, other programs which use identical methodologies sometimes yield very different results. The choice of ref. frame rather than the math. formulation has the greater effect on calcd. parameters. Any factor which influences the ref. frame, such as fitting or not fitting std. bases to the exptl. derived coordinates, will have a noticeable effect on both complementary base pair and dimer step parameters. [on SciFinder (R)]
BibTeX: @article{RefWorks:397, author = {Xiang-Jun Lu and Marla S. Babcock and Wilma K. Olson}, title = {Overview of nucleic acid analysis programs.}, journal = {Journal of Biomolecular Structure & Dynamics}, year = {1999}, volume = {16}, number = {4}, pages = {833-843}, note = {Copyright (C) 2007 ACS on SciFinder (R)); Section Code: 9-0; CODEN: JBSDD6} }
Lu, X. & Olson, W. K.	3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. [Abstract] [BibTeX]	2003	Nucleic acids research	article
Abstract: We present a comprehensive software package, 3DNA, for the anal., reconstruction and visualization of three-dimensional nucleic acid structures. Starting from a coordinate file in Protein Data Bank (PDB) format, 3DNA can handle antiparallel