Using molecular dynamics simulations to evaluate active designs of cephradine hydrolase by molecular mechanics/Poisson-Boltzmann surface area and molecular mechanics/generalized Born surface area methods.

ABSTRACT: The poor predictive accuracy of current computational enzyme design methods has led to low success rates of producing highly active variants that target non-natural substrates. In this report, a quantitative assessment approach based on molecular dynamics (MD) simulations was developed to eliminate false-positive enzyme designs at the computational stage. Taking cephradine hydrolase as an example, the apparent Michaelis binding constant (K _m) and catalytic efficiency (k _cat/K _m) of designed variants were correlated with binding free energies and activation energy barriers, respectively, as calculated by molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) and molecular mechanics/generalized Born surface area (MM/GBSA) methods wi

SUBMITTER: Xue J 

PROVIDER: S-EPMC9064048 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature