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Research

Summary

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: (1) 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; (2) computer simulation of the DNA conformational transitions; (3) improved procedures to analyze local structural morphology and to model the effects of base sequence and electrostatics on macromolecular flexibility; (4) new computational models of protein-nucleic acid interactions.

DNA conformational transitions

Visualization of the conformational transition of a 200 bp naturally closed circular DNA molecule from the circular form to the figure-8 form. The transition pathway is deduced by combining the lowest frequency bending normal mode of a torsionally stressed duplex about its minimum energy configuration and the corresponding mode of the same DNA with respect to the minimum energy figure-8 state. To see an animation please click on movie. (Image based on normal mode calculations performed by Dr. Atsushi Matsumoto)

DNA four-way junctions

Space-filling model of a square planar DNA four-way junction. The crossover single strands are colored blue and red. The other two single strands kinked at the central site are represented in green and yellow. To see an animation of open DNA four-way junctions moving back and forth from a square planar to a stacked form please click on movie. (Image based on molecular modeling studies performed by Dr. A. R. Srinivasan and Professor Wilma K. Olson).

Awards & Honors

Olson, Wilma K., Gorin, Andrey A., Lu, Xiang-Jun, Hock, Lynette M., and Zhurkin, Victor B., "DNA Sequence-dependent Deformability Deduced from Protein-DNA Crystal Complexes," Proc. Natl. Acad. Sci., USA 95, 11163-11168 (1998).

Martino, Jennifer A., Katritch, Vsevolod, and Olson, Wilma K., "Influence of Nucleosome Structure on the Three-dimensional Folding of Idealized Minichromosomes," Structure 7, 1009-1022 (1999).

Lu, Xiang-Jun, Shakked, Zippora, and Olson, Wilma K., "A-form Conformational Motifs in Ligand-bound DNA Structures," J. Mol. Biol. 300, 819-840 (2000).

Olson, Wilma K. and Zhurkin, Victor B, "Modeling DNA Deformations," Current Opinion in Structural Biology, 10, 286-297 (2000).

Katritch, Vsevolod, Bustamante, Carlos, and Olson Wilma K., "Pulling Chromatin Fibers: Computer Simulations of Direct Physical Micromanipulations" J. Mol. Biol. 295, 29-40 (2000).

Olson, Wilma K., Lu, Xiang-Jun, Westbrook, John, Bansal, Manju, Burley, Stephen K., Dickerson, Richard E., Gerstein, Mark, Harvey, Stephen C., Heinemann, Udo, Neidle, Stephen, Shakked, Zippora, Suzuki, Masashi, Tung, Chang-Shung, Sklenar, Heinz, Westhof, Eric, Wolberger, Cynthia, and Berman, Helen M., "A Standard Reference Frame for the Description f Nucleic Acid Base-pair Geometry," J. Mol. Biol. 313, 229-237 (2001).

Kosikov, Konstantin M., Gorin, Andrey A., Lu, Xiang-Jun, Olson, Wilma K., and Manning, Gerald S., "Bending of DNA by Asymmetric Charge Neutralization: All-atom Energy Simulations," J. Am. Chem. Soc., 124, 4838-4847 (2002).

Matsumoto, Atsushi and Olson, Wilma K. "Sequence-dependent Motions of DNA: A Normal Mode Analysis at the Base-pair Level," Biophys. J. 83, 22-41 (2002).

Wang, Lihua, Srinivasan, A. R., Hingerty, Brian E., Olson, Wilma K., and Suse Broyde, Accurate Representation of B-DNA Double Helical Structure with Implicit Solvent and Counterions," Biophys. J. 83, 382-406 (2002).

Fenley, Marcia O., Chua, Kiat, Boschitsch, Alexander H., and Olson, Wilma K., "A Fast Adaptive Multipole Method for the Computation of Electrostatic Energy in Simulations of Polyelectrolyte DNA," J. Comp. Chem. 17, 976-991 (1996).

Katritch, Vsevolod, Olson, Wilma K., Pieranski, Piotr, Dubochet, Jacques, and Stasiak, Andrzej, "Properties of Ideal Composite Knots," Nature, 388, 148-151 (1997).

Liu, Guohua, Schlick, Tamar, Olson, Andrew J., and Olson, Wilma K. "Dynamics of Fourier Series-represented DNA Supercoils," Biophys. J., 73, 1742-1762 (1997).

Martino, Jennifer A. and Olson, Wilma K., "Modeling Protein-induced Configurational Changes in DNA Minicircles," Biopolymers 41, 419-430 (1997).

Olson, Wilma K.. "Simulating DNA at Low Resolution," Current Opinion in Structural Biology 6, 242-256 (1996).

Westcott, Timothy P., Tobias, Irwin, and Olson, Wilma K., "Modeling Self-Contact Forces in the Elastic Theory of DNA Supercoiling," J. Chem. Phys. 107, 3967-3980 (1997).