Enzymatic DNA base flipping mechanism examined via nudged elastic band simulations

COMP 236

Christina Bergonzo, cbergonzo@gmail.com, Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11790, Arthur J. Campbell, ajcampbell@anchovy.org, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, Carlos De los Santos, cds@pharm.sunysb.edu, Department of Pharmacological Sciences, State University of New York, Stony Brook, NY 11794, Arthur P. Grollman, apg@pharm.stonybrook.edu, Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794-8651, and Carlos Simmerling, carlos.simmerling@stonybrook.edu, Department of Chemistry, SUNY Stony Brook, Stony Brook, NY 11794-3400.
A central mechanism of 8-oxoguanine repair by the glycosylase Fpg concerns the path by which the damaged base is everted from an intrahelical position to an extrahelical position in the active site of the enzyme. To elucidate the effect of mutations, which confer a loss of function, on the Fpg-DNA complex, we present a study of the conformational changes which occur during this base eversion process as modeled using the nudged elastic band (NEB) model. The NEB model determines the minimum potential energy pathway of a conformational transition based on endpoint configurations. Decoupling of the forces applied to each image on the chain results in a minimum energy path. The implementation of the NEB model on the explicitly solvated Fpg-DNA system (60000+ atoms), will be discussed.

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

8:00 PM-10:00 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- Hall D, Sci-Mix

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009