Exploring the challenges of computational enzyme design by rebuilding the active site of a dehalogenase.

ABSTRACT: Rational enzyme design presents a major challenge that has not been overcome by computational approaches. One of the key challenges is the difficulty in assessing the magnitude of the maximum possible catalytic activity. In an attempt to overcome this challenge, we introduce a strategy that takes an active enzyme (assuming that its activity is close to the maximum possible activity), design mutations that reduce the catalytic activity, and then try to restore that catalysis by mutating other residues. Here we take as a test case the enzyme haloalkane dehalogenase (DhlA), with a 1,2-dichloroethane substrate. We start by demonstrating our ability to reproduce the results of single mutations. Next, we design mutations that reduce the enzyme activity and finally design double mutations that ar

SUBMITTER: Jindal G 

PROVIDER: S-EPMC6329970 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature