Mary I. Bunting Professor of Chemistry
Research Synopsis: Theoretical studies of nucleic acid conformation, properties, and interactions
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).
Matsumoto, Atsushi, Tobias, Irwin, and Olson, Wilma K., “Normal Mode Analysis of Circular DNA at the Base pair Level. I. Comparison of Computed Motions with Predicted Behavior of an Ideal Elastic Rod,” J. Chem. Theor. Comp. 1, 117-129 (2005). Matsumoto, Atsushi, Tobias, Irwin, and Olson, Wilma K., “Normal Mode Analysis of Circular DNA at the Base pair Level. II. Large-scale Configurational Transformation of a Naturally Curved Molecule,” J. Chem. Theor. Comp. 1, 130-142 (2005).
Ge, Wei, Schneider, Bohdan, and Olson, Wilma K., “Knowledge-based Elastic Potentials for Docking Drugs or Proteins with Nucleic Acids,” Biophys. J. 88, 1166-1190 (2005).
Czapla, Luke, Swigon, David, and Olson, Wilma K., “Sequence-dependent Monte Carlo Simulations of DNA Ring Closure,” J. Chem. Theor. Comp. 2, 685-695 (2006).
Swigon, David, Coleman, Bernard D., and Olson, Wilma K., “Modeling the Lac Repressor-operator Assembly. I. The Influence of DNA Looping on Lac Repressor Conformation,” Proc. Natl. Acad. Sci., USA 103, 9879-9884 (2006).
Olson, Wilma K., Colasanti, Andrew V., Li, Yun , Ge, Wei , Zheng, Guohui, and Zhurkin, Victor B., “DNA Simulation Benchmarks as Revealed by X-ray Structures” in Computational Studies of RNA and DNA, Jiri Sponer and Filip Lankas , Eds., Springer, Dordrecht, The Netherlands, pp.235-257 (2006).
Matsumoto, Atsushi and Olson, Wilma K., “Predicted Effects of Local Conformational Coupling on the Torsional Properties of Single DNA Molecules,” Multiscale Modeling & Simulation, 5, 1227-1247 (2006).
Tolstorukov, Michael Y., Colasanti, Andrew V., McCandlish, David M., Olson, Wilma K., and Zhurkin, Victor B., “A Novel Roll-and-Slide Mechanism of DNA Folding in Chromatin: Implications for Nucleosome Positioning,” J. Mol. Biol. 371, 725-738 (2007).
Tolstorukov, Michael Y., Choudhary, Vidhu, Olson, Wilma K., Zhurkin, Victor B., and Park, Peter J., “nuScore: A Web Interface for Nucleosome-positioning Predictions,” Bioinformatics 24, 1456-1458 (2008).
Olson, Wilma K., Colasanti, Andrew V., Lu, Xiang-Jun, and Zhurkin, Victor B. “Physico-chemical Properties of Nucleic Acids: Character and Recognition of Watson-Crick Base Pairs,” in Wiley Encyclopedia of Chemical Biology, John Wiley & Sons, New York, doi:10.1002/9780470048672.wecb452 (2008).
Lu, Xiang Jun and Olson, Wilma K. “3DNA: A Versatile, Integrated Software System for the Analysis, Rebuilding, and Visualization of Three-dimensional Nucleic-acid Structures,” Nature Protocols 3, 1213-1227 (2008).
Czapla, Luke, Swigon, David, and Olson, Wilma K., “Effects of the Nucleoid Protein HU on the Structure, Flexibility, and Ring-closure Properties of DNA Deduced from Monte-Carlo Simulations,” J. Mol. Biol. 382, 353-370 (2008).
Swigon, David and Olson, Wilma K., “Mesoscale Modeling of Multi-protein-DNA Assemblies: The Role of the Catabolic Activator Protein in Lac-repressor-mediated Looping,” Intl. J. Non-linear Mechanics, doi:10.1016/j.ijnonlinmec.2008.07.003 (2008).
Karymov, Mikhail A., Mathivanan, Chinnaraj, Bogdanov, Aleksey, Srinivasan, Annankoil R., Olson, Wilma K., and Lyubchenko, Yuri L., “Structure, Dynamics and Branch Migration of DNA Holliday Junction: A Single-molecule Fluorescence and Modeling Study” Biophys. J. 95, 4372-4383 (2008).
Olson, Wilma K., Colasanti, Andrew V., Czapla, Luke, and Zheng, Guohui, “Insights into the Sequence-dependent Macromolecular Properties of DNA from Base-pair Level Modeling,” in Coarse-Graining of Condensed Phase and Biomolecular Systems, Gregory A. Voth, Ed., CRC Press, Taylor and Francis Group, Boca Raton, FL, pp. 205-223 (2008).
Xin, Yurong, and Olson, Wilma K., “BPS: A Database of RNA Base-pair Structures,” Nucleic Acids Res., 1-6, doi:10.1093/nar/gkn676 (2008).