Introduction

The goal of our research is to understand the influence of chemical architecture on the conformation, properties, and interactions of nucleic acids. The work attempts to clarify the role of local structure (e.g., primary base sequence, polyelectrolyte sugar-phosphate backbone) and ligand binding (e.g., proteins, drugs) on the overall folding of DNA and RNA. A second goal is to uncover structural details of nucleic acid structural transitions, such as those involving different DNA duplexes. The research combines a variety of computational approaches (Monte Carlo and molecular dynamics simulations, potential energy calculations, developments and applications of polymer chain statistics, finite element analysis, systematic molecular modeling) with new developments in polymer theory. Problems of current interest include:

• New computational methods to generate and analyze the folding of RNA, the junctions of DNA and RNA helices, and the sequence-dependent supercoiling of the DNA double helix.
• Computer simulation of the DNA conformational transitions.
• Improved procedures to analyze local structural morphology and to model the effects of base sequence and electrostatics on macromolecular flexibility.
• New computational models of protein-nucleic acid interactions.