Protein oligomer structure prediction using GALAXY in CASP14

• Published in: Proteins, structure, function, and bioinformatics Vol. 89; no. 12; pp. 1844 - 1851
• Main Authors: Park, Taeyong, Woo, Hyeonuk, Yang, Jinsol, Kwon, Sohee, Won, Jonghun, Seok, Chaok
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-12-2021; Wiley Subscription Services, Inc
• Subjects: Biomolecules; Computational Biology; Computer applications; Crystal structure; Docking; Domains; Information processing; Models, Molecular; Molecular Docking Simulation; Monomers; Oligomers; Predictions; protein complex structure refinement; Protein Conformation; Protein Folding; protein hetero‐oligomer structure prediction; protein homo‐oligomer structure prediction; Protein structure; protein structure prediction; Protein Subunits - chemistry; Protein Subunits - metabolism; Proteins; Proteins - chemistry; Proteins - metabolism; protein–protein docking; Sequence Analysis, Protein; Software; protein homo-oligomer structure prediction; protein complex structure refinement; protein hetero-oligomer structure prediction; protein structure prediction; protein-protein docking
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.26203

Proteins perform their functions by interacting with other biomolecules. For these interactions, proteins often form homo‐ or hetero‐oligomers as well. Thus, oligomer protein structures provide important clues regarding the biological roles of proteins. To this end, computational prediction of oligomer structures may be a useful tool in the absence of experimentally resolved structures. Here, we describe our server and human‐expert methods used to predict oligomer structures in the CASP14 experiment. Examples are provided for cases in which manual domain‐splitting led to improved oligomeric domain structures by ab initio docking, automated oligomer structure refinement led to improved subunit orientation and terminal structure, and manual oligomer modeling utilizing literature information generated a reasonable oligomer model. We also discussed the results of post‐prediction docking calculations with AlphaFold2 monomers as input in comparison to our blind prediction results. Overall, ab initio docking of AlphaFold2 models did not lead to better oligomer structure prediction, which may be attributed to the interfacial structural difference between the AlphaFold2 monomer structures and the crystal oligomer structures. This result poses a next‐stage challenge in oligomer structure prediction after the success of AlphaFold2. For successful protein assembly structure prediction, a different approach that exploits further evolutionary information on the interface and/or flexible docking taking the interfacial conformational flexibilities of subunit structures into account is needed.