title: Modeling and predicting interactions between the human amphiphysin SH3 domains and their peptide ligands based on amino acid information.
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.
authors.affiliation: Department of Dermatovenereology-First Affiliated Hospital of Wenzhou Medical College, Institute of Dermatovenereology, Wenzhou Medical College, Wenzhou 325000, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
authors.forename: Rongying
authors.initials: R
authors.lastname: Ou
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Lin
authors.forename: Mao
authors.initials: M
authors.lastname: Shu
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009842:Oligopeptides; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D018909:src Homology Domains / Q000187:drug effects*
chemical_list: D000596:Amino Acids; D008024:Ligands; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; C075637:amphiphysin