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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

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

Revista

Título: Journal of Chemical Information and Modeling

Vol. 63

Páginas: 20-26

ISSN: 1549-9596

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7