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Engineering DszC Mutants from Transition State Macrodipole Considerations and Evolutionary Sequence Analysis.

ABSTRACT: We describe an approach to identify enzyme mutants with increased turnover using the enzyme DszC as a case study. Our approach is based on recalculating the barriers of alanine mutants through single-point energy calculations at the hybrid QM/MM level in the wild-type reactant and transition state geometries. We analyze the difference in the electron density between the reactant and transition state to identify sites/residues where electrostatic interactions stabilize the transition state over the reactants. We also assess the insertion of a unit probe charge to identify positions in which the introduction of charged residues lowers the barrier.

SUBMITTER: Neves RPP

PROVIDER: S-EPMC9832474 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Engineering DszC Mutants from Transition State Macrodipole Considerations and Evolutionary Sequence Analysis.

Neves Rui P P RPP Ramos Maria J MJ Fernandes Pedro A PA

Journal of chemical information and modeling 20221219 1

We describe an approach to identify enzyme mutants with increased turnover using the enzyme DszC as a case study. Our approach is based on recalculating the barriers of alanine mutants through single-point energy calculations at the hybrid QM/MM level in the wild-type reactant and transition state geometries. We analyze the difference in the electron density between the reactant and transition state to identify sites/residues where electrostatic interactions stabilize the transition state over t ...[more]

PMID: 36534708

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