Towards quantitative computer-aided studies of enzymatic enantioselectivity: the case of Candida antarctica lipase A.

ABSTRACT: The prospect for consistent computer-aided refinement of stereoselective enzymes is explored by simulating the hydrolysis of enantiomers of an α-substituted ester by wild-type and mutant Candida antarctica lipase A, using several strategies. In particular, we focused on the use of the empirical valence bond (EVB) method in a quantitative screening for enantioselectivity, and evaluate both k(cat) and k(cat)/K(M) of the R and S stereoisomers. We found that an extensive sampling is essential for obtaining converging results. This requirement points towards possible problems with approaches that use a limited conformational sampling. However, performing the proper sampling appears to give encouraging results and to offer a powerful tool for the computer-aided design of enantioselective enzymes

SUBMITTER: Frushicheva MP 

PROVIDER: S-EPMC3414264 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature