Computational design of an amidase by combining the best electrostatic features of two promiscuous hydrolases.

ABSTRACT: While there has been emerging interest in designing new enzymes to solve practical challenges, computer-based options to redesign catalytically active proteins are rather limited. Here, a rational QM/MM molecular dynamics strategy based on combining the best electrostatic properties of enzymes with activity in a common reaction is presented. The computational protocol has been applied to the re-design of the protein scaffold of an existing promiscuous esterase from Bacillus subtilis Bs2 to enhance its secondary amidase activity. After the alignment of Bs2 with a non-homologous amidase Candida antarctica lipase B (CALB) within rotation quaternions, a relevant spatial aspartate residue of the latter was transferred to the former as a means to favor the electrostatics of transit

SUBMITTER: Galmes MA 

PROVIDER: S-EPMC9067594 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature