SPEACH_AF: Sampling protein ensembles and conformational heterogeneity with Alphafold2.

ABSTRACT: The unprecedented performance of Deepmind's Alphafold2 in predicting protein structure in CASP XIV and the creation of a database of structures for multiple proteomes and protein sequence repositories is reshaping structural biology. However, because this database returns a single structure, it brought into question Alphafold's ability to capture the intrinsic conformational flexibility of proteins. Here we present a general approach to drive Alphafold2 to model alternate protein conformations through simple manipulation of the multiple sequence alignment via in silico mutagenesis. The approach is grounded in the hypothesis that the multiple sequence alignment must also encode for protein structural heterogeneity, thus its rational manipulation will enable Alphafold2 to sample alternate co

SUBMITTER: Stein RA 

PROVIDER: S-EPMC9436118 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature