On possible pitfalls in ab initio quantum mechanics/molecular mechanics minimization approaches for studies of enzymatic reactions.

ABSTRACT: Reliable studies of enzymatic reactions by combined quantum mechanics/molecular mechanics (QM/MM) approaches, with an ab initio description of the quantum region, presents a major challenge to computational chemists. The main problem is the need for a very large computer time for the evaluation of the QM energy, which in turn makes it extremely challenging to perform proper configurational sampling. A seemingly reasonable alternative is to perform energy minimization studies of the type used in gas-phase ab initio studies. However, it is hard to see why such an approach should give reliable results in protein active sites. To examine the problems with energy minimization QM/MM approaches, we chose the hypothetical reaction of a metaphosphate ion with water in the Ras.GAP complex. This hypo

SUBMITTER: Klahn M 

PROVIDER: S-EPMC1514348 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature