Topological links in predicted protein complex structures reveal limitations of AlphaFold.

ABSTRACT: AlphaFold is making great progress in protein structure prediction, not only for single-chain proteins but also for multi-chain protein complexes. When using AlphaFold-Multimer to predict protein‒protein complexes, we observed some unusual structures in which chains are looped around each other to form topologically intertwining links at the interface. Based on physical principles, such topological links should generally not exist in native protein complex structures unless covalent modifications of residues are involved. Although it is well known and has been well studied that protein structures may have topologically complex shapes such as knots and links, existing methods are hampered by the chain closure problem and show poor performance in identifying topologically linked structures i

SUBMITTER: Hou Y 

PROVIDER: S-EPMC10613300 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature