In silico quantitative prediction of peptides binding affinity to human MHC molecule: an intuitive quantitative structure–activity relationship approach

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Abstract
In this paper, we have handpicked 23 kinds of electronic properties, 37 kinds of steric properties, 54 kinds of hydrophobic properties and 5 kinds of hydrogen bond properties from thousands of amino acid structural and property parameters. Principal component analysis (PCA) was applied on these parameters and thus ten score vectors involving significant nonbonding properties of 20 coded amino acids were yielded, called the divided physicochemical property scores (DPPS) of amino acids. The DPPS descriptor was then used to characterize the structures of 152 HLA-A*0201-restricted CTL epitopes, and significant variables being responsible for the binding affinities were selected by genetic algorithm, and a quantitative structure–activity relationship (QSAR) model by partial least square was established to predict the peptide-HLA-A*0201 molecule interactions. Statistical analysis on the resulted DPPS-based QSAR models were consistent well with experimental exhibits and molecular graphics display. Diversified properties of the different residues in binding peptides may contribute remarkable effect to the interactions between the HLA-A*0201 molecule and its peptide ligands. Particularly, hydrophobicity and hydrogen bond of anchor residues of peptides may have a significant contribution to the interactions. The results showed that DPPS can well represent the structural characteristics of the antigenic peptides and is a promising approach to predict the affinities of peptide binding to HLA-A*0201 in a efficient and intuitive way. We expect that this physical-principle based method can be applied to other protein–peptide interactions as well.