title: HLA-DP2 binding prediction by molecular dynamics simulations.
abstract: Major histocompatibility complex (MHC) II proteins bind peptide fragments derived from pathogen antigens and present them at the cell surface for recognition by T cells. MHC proteins are divided into Class I and Class II. Human MHC Class II alleles are grouped into three loci: HLA-DP, HLA-DQ, and HLA-DR. They are involved in many autoimmune diseases. In contrast to HLA-DR and HLA-DQ proteins, the X-ray structure of the HLA-DP2 protein has been solved quite recently. In this study, we have used structure-based molecular dynamics simulation to derive a tool for rapid and accurate virtual screening for the prediction of HLA-DP2-peptide binding. A combinatorial library of 247 peptides was built using the "single amino acid substitution" approach and docked into the HLA-DP2 binding site. The complexes were simulated for 1 ns and the short range interaction energies (Lennard-Jones and Coulumb) were used as binding scores after normalization. The normalized values were collected into quantitative matrices (QMs) and their predictive abilities were validated on a large external test set. The validation shows that the best performing QM consisted of Lennard-Jones energies normalized over all positions for anchor residues only plus cross terms between anchor-residues.
authors: School of Pharmacy, Medical University of Sofia, Sofia 1000, Bulgaria. idoytchinova@pharmfac.net
authors: Irini
authors: I
authors: Doytchinova
authors: Peicho
authors: P
authors: Petkov
authors: Ivan
authors: I
authors: Dimitrov
authors: Mariyana
authors: M
authors: Atanasova
authors: Darren R
authors: DR
authors: Flower
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites / Q000276:immunology; D018360:Crystallography, X-Ray; D059868:HLA-DP beta-Chains / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008285:Major Histocompatibility Complex; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019151:Peptide Library; D011485:Protein Binding
chemical_list: D059868:HLA-DP beta-Chains; C083176:HLA-DPw2 antigen; D019151:Peptide Library