Ab initio quantum mechanical/molecular mechanical molecular dynamics simulation of enzyme catalysis: the case of histone lysine methyltransferase SET7/9.

ABSTRACT: To elucidate enzyme catalysis through computer simulation, a prerequisite is to reliably compute free energy barriers for both enzyme and solution reactions. By employing on-the-fly Born-Oppenheimer molecular dynamics simulations with the ab initio quantum mechanical/molecular mechanical approach and the umbrella sampling method, we have determined free energy profiles for the methyl-transfer reaction catalyzed by the histone lysine methyltransferase SET7/9 and its corresponding uncatalyzed reaction in aqueous solution, respectively. Our calculated activation free energy barrier for the enzyme catalyzed reaction is 22.5 kcal/mol, which agrees very well with the experimental value of 20.9 kcal/mol. The difference in potential of mean force between a corresponding prereaction state and the t

SUBMITTER: Wang S 

PROVIDER: S-EPMC2527688 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature