{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xue J"],"funding":["Ministry of Science and Technology of the People&apos;s Republic of China","National Natural Science Foundation of China"],"pagination":["13868-13877"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9064048"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(24)"],"pubmed_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 (<i>K</i> <sub>m</sub>) and catalytic efficiency (<i>k</i> <sub>cat</sub>/<i>K</i> <sub>m</sub>) 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"],"journal":["RSC advances"],"pubmed_title":["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."],"pmcid":["PMC9064048"],"funding_grant_id":["21476123","2012AA021204","21878170"],"pubmed_authors":["Zhu Y","Huang X","Xue J"],"additional_accession":[]},"is_claimable":false,"name":"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.","description":"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 (<i>K</i> <sub>m</sub>) and catalytic efficiency (<i>k</i> <sub>cat</sub>/<i>K</i> <sub>m</sub>) 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","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Apr","modification":"2026-05-30T15:17:31.047Z","creation":"2025-04-04T10:01:57.53Z"},"accession":"S-EPMC9064048","cross_references":{"pubmed":["35519543"],"doi":["10.1039/c9ra02406a"]}}