51. Modeling and predicting interactions between the human amphiphysin SH3 domains and their peptide ligands based on amino acid information
- Author
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Li Yang, Zhihua Lin, Rongying Ou, Jianfeng Cai, Mao Shu, and Yun-Sheng Xu
- Subjects
Steric effects ,Quantitative structure–activity relationship ,Stereochemistry ,Protein Conformation ,Quantitative Structure-Activity Relationship ,Peptide ,Nerve Tissue Proteins ,Ligands ,Biochemistry ,SH3 domain ,src Homology Domains ,Structural Biology ,Drug Discovery ,Humans ,Amino Acid Sequence ,Amino Acids ,Molecular Biology ,Peptide ligand ,Pharmacology ,chemistry.chemical_classification ,Hydrogen bond ,Chemistry ,Organic Chemistry ,Hydrogen Bonding ,General Medicine ,Amino acid ,Amphiphysin ,Molecular Medicine ,Oligopeptides - 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 P2 and P−3 (including P2 and P−3) of the decapeptide (P4P3P2P1P0P−1P−2P−3P−4P−5) may contribute remarkable effect to the interactions between the SH3 domain and decapeptides. Particularly, hydrogen bond and steric properties of P2 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.
- Published
- 2010