title: Toward the quantitative prediction of T-cell epitopes: coMFA and coMSIA studies of peptides with affinity for the class I MHC molecule HLA-A*0201.
abstract: A set of 102 peptides with affinity for the class I MHC HLA-A0201 molecule was subjected to three-dimensional quantitative structure-affinity relationship (3D QSAR) studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). A test set of 50 peptides was used to determine the predictive value of the models. The CoMFA models gave q(2) and r(2)pred below 0.5. The best CoMSIA model has q(2) = 0.542 and r(2)pred = 0.679, and includes hydrophobic, steric, and H-bond donor fields. The hydrophobic interactions play a dominant role in peptide-MHC molecule binding. CoMSIA coefficient contour maps were used to analyze the structural features of the peptides accounting for the affinity in terms of the three positively contributing physicochemical properties: local hydrophobicity, steric bulk and hydrogen-bond-donor ability.
authors.affiliation: Edward Jenner Institute for Vaccine Research, Compton, Berkshire, RG20 7NN, UK. irini.doytchinova@jenner.ac.uk
authors.forename: I A
authors.initials: IA
authors.lastname: Doytchinova
authors.forename: D R
authors.initials: DR
authors.lastname: Flower
mesh_terms: D000595:Amino Acid Sequence; D000939:Epitopes; D015234:HLA-A Antigens / Q000737:chemistry*; D015789:HLA-A2 Antigen; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides