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
- 19 September 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 44 (22) , 3572-3581
- https://doi.org/10.1021/jm010021j
Abstract
A set of 102 peptides with affinity for the class I MHC HLA-A*0201 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 q2 and r2pred below 0.5. The best CoMSIA model has q2 = 0.542 and r2pred = 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.Keywords
This publication has 43 references indexed in Scilit:
- Structure‐based prediction of binding peptides to MHC class I molecules: Application to a broad range of MHC allelesProtein Science, 2000
- Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2.1 binding positions.Journal of Clinical Investigation, 1998
- Two complementary methods for predicting peptides binding major histocompatibility complex moleculesJournal of Molecular Biology, 1997
- Molecular Dynamics Simulation of MHC-Peptide Complexes as a Tool for Predicting Potential T Cell EpitopesBiochemistry, 1994
- Peptide binding to the most frequent HLA-A class I alleles measured by quantitative molecular binding assaysMolecular Immunology, 1994
- Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 moleculesCell, 1993
- Identification of self peptides bound to purified HLA-B27Nature, 1991
- Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC moleculesNature, 1991
- Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolutionJournal of Molecular Biology, 1991
- Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Conventional QSAR StudiesQuantitative Structure-Activity Relationships, 1988