Analysis of Correlation Effects of Double Mutations in Enzymes: A Revised Residual-Contact Network Clique Model.
Int J Mol Sci
; 25(16)2024 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-39201800
ABSTRACT
The relationship between amino acid mutations and enzyme bioactivity is a significant challenge in modern bio-industrial applications. Despite many successful designs relying on complex correlations among mutations at different enzyme sites, the underlying mechanisms of these correlations still need to be explored. In this study, we introduced a revised version of the residual-contact network clique model to investigate the additive effect of double mutations based on the mutation occurrence topology, secondary structures, and physicochemical properties. The model was applied to a set of 182 double mutations reported in three extensively studied enzymes, and it successfully identified over 90% of additive double mutations and a majority of non-additive double mutations. The calculations revealed that the mutation additivity depends intensely on the studied mutation sites' topology and physicochemical properties. For example, double mutations on irregular secondary structure regions tend to be non-additive. Our method provides valuable tools for facilitating enzyme design and optimization. The code and relevant data are available at Github.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enzimas
/
Mutação
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Suíça