Rosetta Energy Analysis of AlphaFold2 models: Point Mutations and Conformational Ensembles.

ABSTRACT: There has been an explosive growth in the applications of AlphaFold2, and other structure prediction platforms, to accurately predict protein structures from a multiple sequence alignment (MSA) for downstream structural analysis. However, two outstanding questions persist in the field regarding the robustness of AlphaFold2 predictions of the consequences of point mutations and the completeness of its prediction of protein conformational ensembles. We combined our previously developed method SPEACH_AF with model relaxation and energetic analysis with Rosetta to address these questions. SPEACH_AF introduces residue substitutions across the MSA and not just within the input sequence. With respect to conformational ensembles, we combined SPEACH_AF and a new MSA subsampling method, AF_cluster,

SUBMITTER: Stein RA 

PROVIDER: S-EPMC10508732 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature