title: A flexible docking approach for prediction of T cell receptor-peptide-MHC complexes.
abstract: T cell receptors (TCRs) are immune proteins that specifically bind to antigenic molecules, which are often foreign peptides presented by major histocompatibility complex proteins (pMHCs), playing a key role in the cellular immune response. To advance our understanding and modeling of this dynamic immunological event, we assembled a protein-protein docking benchmark consisting of 20 structures of crystallized TCR/pMHC complexes for which unbound structures exist for both TCR and pMHC. We used our benchmark to compare predictive performance using several flexible and rigid backbone TCR/pMHC docking protocols. Our flexible TCR docking algorithm, TCRFlexDock, improved predictive success over the fixed backbone protocol, leading to near-native predictions for 80% of the TCR/pMHC cases among the top 10 models, and 100% of the cases in the top 30 models. We then applied TCRFlexDock to predict the two distinct docking modes recently described for a single TCR bound to two different antigens, and tested several protein modeling scoring functions for prediction of TCR/pMHC binding affinities. This algorithm and benchmark should enable future efforts to predict, and design of uncharacterized TCR/pMHC complexes.
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Pierce
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
mesh_terms: D000465:Algorithms; D006649:Histocompatibility Antigens / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*
chemical_list: D006649:Histocompatibility Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell