Biomolecular Simulation of Base Excision Repair and Protein Signaling

The goal of the Biomolecular Simulation of Base Excision Repair and Protein Signaling project is to enhance our understanding of the mechanism of human polymerase-β, one of the key enzymes in base excision repair (BER) and the cell-signaling enzymes cyclic-AMP-dependent protein kinase. This work used molecular modeling and simulation studies to specifically focus on the • dynamics of DNA and damaged DNA • dynamics and energetics of base flipping in DNA • mechanism and fidelity of nucleotide insertion by BER enzyme human polymerase-β • mechanism and inhibitor design for cyclic-AMP-dependent protein kinase. Molecular dynamics simulations and electronic structure calculations have been performed using the computer resources at the Molecular Science Computing Facility at the Environmental Molecular Sciences Laboratory. List of all team members Team Leader Name: T. P. Straatsma Position: Associate Division Director, Computational Biology and Bioinformatics Computational Sciences and Mathematics Division Institution: Pacific Northwest National Laboratory Address: P.O.Box 999, MS K7-90 Richland, WA 99352 Telephone: (509) 375-2802 Facsimile: (509) 375-6631 Email: [email protected] Team Member 2 Name: J. A. McCammon Position: Joseph E. Mayer Professor of Theoretical Chemistry Institution: University of California at San Diego Department of Chemistry and Biochemistry, and Department of Pharmacology Address: 9500 Gilman Drive, M/C 0365 La Jolla, CA 92093-0365 Telephone: (858) 534-2905 Facsimile: (858) 534-7042 Email: [email protected] Team Member 3 Name: J. H. Miller Position: Associate Professor