Coevolution-based prediction of key allosteric residues for protein function regulation.

ABSTRACT: Allostery is fundamental to many biological processes. Due to the distant regulation nature, how allosteric mutations, modifications, and effector binding impact protein function is difficult to forecast. In protein engineering, remote mutations cannot be rationally designed without large-scale experimental screening. Allosteric drugs have raised much attention due to their high specificity and possibility of overcoming existing drug-resistant mutations. However, optimization of allosteric compounds remains challenging. Here, we developed a novel computational method KeyAlloSite to predict allosteric site and to identify key allosteric residues (allo-residues) based on the evolutionary coupling model. We found that protein allosteric sites are strongly coupled to orthosteric site compared

SUBMITTER: Xie J 

PROVIDER: S-EPMC9981151 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature