Abstract
In this paper, VHESH, which was a novel set of amino acid descriptors including hydrophobic, electronic, steric, and hydrogen bond contribution properties, were proposed to characterize the structures of the decapeptides binding the human amphiphysin‐1 Src homology 3 (SH3) domains, and QSAR model was constructed by partial least square (PLS) with genetic algorithm‐variable selection. It was found that diversified properties of the residues between P~2~ and P~−3~ (including P~2~ and P~−3~) of the decapeptide (P~4~P~3~P~2~P~1~P~0~P~−1~P~−2~P~−3~P~−4~P~−5~) may contribute remarkable effect to the interactions between the SH3 domain and decapeptides. Particularly, hydrogen bond and steric properties of P~2~ and electronic properties, steric properties of P~−3~ may provide relatively large positive contributions to the interactions. Based on the GA‐PLS model, a series of decapeptides, with relatively high binding affinities were designed. These results showed that VHESH descriptors can well represent the decapeptides. Furthermore, the model obtained, which showed low computational complexity, correlated VHESH descriptors with the binding affinities as well as that VHESH may also be applied in QSAR studies of peptides. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.