title: A comparative molecular similarity index analysis (CoMSIA) study identifies an HLA-A2 binding supermotif.
abstract: The 3D-QSAR CoMSIA technique was applied to a set of 458 peptides binding to the five most widespread HLA-A2-like alleles: A*0201, A*0202, A*0203, A*0206 and A*6802. Models comprising the main physicochemical properties (steric bulk, electron density, hydrophobicity and hydrogen-bond formation abilities) were obtained with acceptable predictivity (q2 ranged from 0.385 to 0.683). The use of coefficient contour maps allowed an A2-supermotif to be identified based on common favoured and disfavoured areas. The CoMSIA definition for the best HLA-A2 binder is as follows: hydrophobic aromatic amino acid at position 1; hydrophobic bulky side chains at positions 2, 6 and 9; non-hydrogen-bond-forming amino acids at position 3; small aliphatic hydrogen-bond donors at position 4; aliphatic amino acids at position 5; small aliphatic side chains at position 7; and small aliphatic hydrophilic and hydrogen-bond forming amino acids at position 8.
authors.affiliation: Edward Jenner Istitute for Vaccine Research, Compton, Berkshire, RG20 7NN, UK.
authors.forename: Irini A
authors.initials: IA
authors.lastname: Doytchinova
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
chemical_list: D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D009842:Oligopeptides