Adaptively biased dynamics study of the excited states of TIM

COMP 200

Sishi Tang, sishi@rci.rutgers.edu and David Case, case@biomaps.rutgers.edu. BioMaPS Institute, Rutgers University, 610 Taylor Rd, Piscataway, NJ 08854
Conformational changes of proteins are closely related to a wide range of protein functions. The "conformation selection" theory suggests that these conformational changes can be facilitated by the coexistence of lowly-populated conformational states with the ground state. In this study, we sought to find and characterize the minor conformational states of triosephosphate isomerase (TIM), which exhibits localized loop motion with catalytic significance. Furthermore, the existing force field and methods of free energy calculation were evaluated. We studied TIM using adaptively biased molecular dynamics (ABMD) simulations. Starting from an “open” loop conformation, a metastable state with “closed” loop conformation was predicted in absence of the ligand. However, comparisons with experimental data suggest that either the force field or procedure for generating the potential of mean force may have systematically underestimated barriers for us-ms transitions in proteins. In addition, comparisons will be made to analogous conformational transitions in other proteins.
 

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

Division of Computers in Chemistry

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