A flexible docking approach for prediction of T cell receptor-peptide-MHC complexes
AuthorsPierce, Brian G.
UMass Chan AffiliationsProgram in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
KeywordsReceptors, Antigen, T-Cell
Genes, MHC Class II
Major Histocompatibility Complex
Molecular Docking Simulation
Biochemistry, Biophysics, and Structural Biology
MetadataShow full item record
AbstractT 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.
SourceProtein Sci. 2013 Jan;22(1):35-46. doi: 10.1002/pro.2181. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/25919
Related ResourcesLink to Article in PubMed