Protein stability models fail to capture epistatic interactions of double point mutations.

ABSTRACT: There is strong interest in accurate methods for predicting changes in protein stability resulting from amino acid mutations to the protein sequence. Recombinant proteins must often be stabilized to be used as therapeutics or reagents, and destabilizing mutations are implicated in a variety of diseases. Due to increased data availability and improved modeling techniques, recent studies have shown advancements in predicting changes in protein stability when a single-point mutation is made. Less focus has been directed toward predicting changes in protein stability when there are two or more mutations. Here, we analyze the largest available dataset of double point mutation stability and benchmark several widely used protein stability models on this and other datasets. We find that additive m

SUBMITTER: Dieckhaus H 

PROVIDER: S-EPMC11659742 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature