Predicting multiple conformations of ligand binding sites in proteins suggests that AlphaFold2 may remember too much.

ABSTRACT: The goal of this paper is predicting the conformational distributions of ligand binding sites using the AlphaFold2 (AF2) protein structure prediction program with stochastic subsampling of the multiple sequence alignment (MSA). We explored the opening of cryptic ligand binding sites in 16 proteins, where the closed and open conformations define the expected extreme points of the conformational variation. Due to the many structures of these proteins in the Protein Data Bank (PDB), we were able to study whether the distribution of X-ray structures affects the distribution of AF2 models. We have found that AF2 generates both a cluster of open and a cluster of closed models for proteins that have comparable numbers of open and closed structures in the PDB and not too many other conformations.

SUBMITTER: Lazou M 

PROVIDER: S-EPMC11621821 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature