Validating computer simulations of enantioselective catalysis; reproducing the large steric and entropic contributions in Candida Antarctica lipase B.

ABSTRACT: The prospect for computer-aided refinement of stereoselective enzymes is further validated by simulating the ester hydrolysis by the wild-type and mutants of CalB, focusing on the challenge of dealing with strong steric effects and entropic contributions. This was done using the empirical valence bond (EVB) method in a quantitative screening of the enantioselectivity, considering both k(cat) and k(cat)/K(M) of the R and S stereoisomers. Although the simulations require very extensive sampling for convergence they give encouraging results and major validation, indicating that our approach offers a powerful tool for computer-aided design of enantioselective enzymes. This is particularly true in cases with large changes in steric effects where alternative approaches may have difficulties in c

SUBMITTER: Schopf P 

PROVIDER: S-EPMC4057354 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature