• HLA-A*0201;
  • non-covalent interaction;
  • peptide;
  • quantitative structure–activity relationship

A structure-based method was used to characterize the non-covalent interactions of HLA-A*0201 with its peptide ligands. In this procedure, protein and peptide atoms were classified into 16 types in terms of their chemical property and local environment, and a 16 × 16 matrix was then defined to describe the interaction mode of 256 atom-pairs between the receptor and ligand in a complex structure. Three biologically related chemical forces as electrostatic, van der Waals, and hydrophobic potentials were separately calculated for each element of the matrix to yield 768 structural descriptors encoding the detailed information about the non-covalent interactions involved in protein–peptide binding. We employed this method to perform quantitative structure–activity relationship (QSAR) study of a data panel consisting of 419 non-apeptides with known binding affinities to HLA-A*0201 protein. Several QSAR models were constructed using partial least square regression (PLS) coupled with or without genetic algorithm (GA)-variable selection, and these models were validated rigorously and investigated systematically by using external test set and one-way analysis of variance. Results show that diverse properties have significant contributions to the HLA-A*0201–peptide binding. Particularly, the hydrophobicity and electrostatic property at the anchor residues of peptides confer a significant specificity and stability for the bound complexes.