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

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Neves, RPP (Author) FCUP; Ramos, MJ (Author) FCUP; Pedro A Fernandes (Author) FCUP

Journal

Title: Journal of Chemical Information and Modeling

Vol. 63

Pages: 20-26

ISSN: 1549-9596

Publisher: American Chemical Society

Indexing

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Other information

Authenticus ID: P-00X-N1E

DOI: 10.1021/acs.jcim.2c01337

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7