Dynamics-based protein network features accurately discriminate neutral and rheostat positions.

ABSTRACT: In some proteins, a unique class of nonconserved positions is characterized by their ability to generate diverse functional outcomes through single amino acid substitutions. Due to their ability to tune protein function, accurately identifying such "rheostat" positions is crucial for protein design, for understanding the impact of mutations observed in humans, and for predicting the evolution of pathogen drug resistance. However, identifying rheostat positions has been challenging, due-in part-to the absence of a clear structural relationship with binding sites. In this study, experimental data from our previous study of the Escherichia coli lactose repressor protein (LacI) was used to identify rheostat positions for which mutations tune in vivo EC₅₀ for the allosteric ligand "I

SUBMITTER: Campitelli P 

PROVIDER: S-EPMC11494493 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature