A Comparative Molecular Similarity Index Analysis (CoMSIA) study identifies an HLA-A2 binding supermotif

Irini A. Doytchinova, Darren R. Flower

Research output: Contribution to journalArticle

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 (q 2 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.
Original languageEnglish
Pages (from-to)535-544
Number of pages10
JournalJournal of Computer-Aided Molecular Design
Volume16
Issue number8-9
DOIs
Publication statusPublished - Aug 2002

Keywords

  • comsia
  • pls
  • a2-supertype

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