Sampling long time scale protein motions: OSRW simulation of active site loop conformational free energies in formyl-CoA:oxalate CoA transferase.

ABSTRACT: X-ray crystallographic snapshots have shown that conformational changes of a tetraglycine loop in the active site of formyl-CoA:oxalate CoA transferase (FRC) play an important role in the catalytic cycle of the enzyme. Orthogonal space random walk (OSRW) simulations have been applied to obtain quantitative computational estimates of the relative free energy of the "open" and "closed" conformations of this loop together with the energetic barrier for interconversion of these states in wild type FRC. These OSRW calculations not only show that the two conformations have similar free energies but also predict a barrier that is consistent with the observed turnover number of the enzyme. In an effort to quantitate the importance of specific residues in the tetraglycine loop, OSRW simulations hav

SUBMITTER: Lee S 

PROVIDER: S-EPMC2877758 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature