A flexible docking approach for prediction of T cell receptor-peptide-MHC complexes.

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TitleA flexible docking approach for prediction of T cell receptor-peptide-MHC complexes.
Publication TypeJournal Article
Year of Publication2013
AuthorsPierce, BG, Weng, Z
JournalProtein Sci
Date Published2013 Jan
KeywordsAlgorithms, Histocompatibility Antigens, Models, Molecular, Peptides, Protein Binding, Receptors, Antigen, T-Cell

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.

Alternate JournalProtein Sci.
PubMed ID23109003
PubMed Central IDPMC3575858
Grant ListGM084884 / GM / NIGMS NIH HHS / United States