title: Peptide Binding Prediction to Five Most Frequent HLA-DQ Proteins - a Proteochemometric Approach.
abstract: Major histocompatibility complex (MHC) proteins class II, are glycoproteins binding within the cell to short peptides with foreign origin, called epitopes, and present them at the cell surface for inspection by T-cells. Apart from presenting foreign antigens, they are able to present also common self-antigens and trigger autoimmune diseases as coeliac disease and diabetes mellitus type 1. The MHC proteins are extremely polymorphic. The polymorphism is located mainly in the peptide binding site. In the present study, we apply a proteochemometric approach to derive a model for prediction of peptide binding to human MHC class II proteins from locus HLA-DQ. Proteochemometrics was applied on 2624 peptides binding to five most frequent HLA-DQ proteins. The sequences of peptides and proteins were described by three z-descriptors relating to hydrophobicity, steric effects and polarity of amino acids. Cross-terms accounting for the protein-peptide interactions also were included. The derived model was validated by external test set of 660 peptides and showed rpred (2) =0.808, AUC=0.965, 92.5 % accuracy at threshold of pIC50 =5.3 and average sensitivity of 83 % among the top 10 % best predicted nonamers. The model is implemented in the server for MHC binding prediction EpiTOP and is freely available at http://www.ddg-pharmfac.net/epitop.
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str, 1000 Sofia, Bulgaria tel: +359 2 9236506.
authors.forename: Ivan
authors.initials: I
authors.lastname: Dimitrov
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str, 1000 Sofia, Bulgaria tel: +359 2 9236506. idoytchinova@pharmfac.net.
authors.forename: Irini
authors.initials: I
authors.lastname: Doytchinova
mesh_terms: D002446:Celiac Disease / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D006683:HLA-DQ Antigens; D010455:Peptides
keywords: Binders; EpiTOP; HLA-DQ; Non-binders; Proteochemometrics; z-Descriptors