A hydrophobic spine stabilizes a surface-exposed α-helix according to analysis of the solvent-accessible surface area

BMC Bioinformatics

Research

Yi-Fan Liou¹  Hui-Ling Huang²  Shinn-Ying Ho² 

[1]Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan

[2]Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan

[3]Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan

关键词: Hydrophobic spine;    Molecular dynamics simulation;    Physicochemical properties;    Protein folding;    Solvent-accessible surface area;    Support vector regression;    Knowledge discovery;   

DOI  :  10.1186/s12859-016-1368-z

来源: Springer

【 摘 要 】

BackgroundMost of hydrophilic and hydrophobic residues are thought to be exposed and buried in proteins, respectively. In contrast to the majority of the existing studies on protein folding characteristics using protein structures, in this study, our aim was to design predictors for estimating relative solvent accessibility (RSA) of amino acid residues to discover protein folding characteristics from sequences.MethodsThe proposed 20 real-value RSA predictors were designed on the basis of the support vector regression method with a set of informative physicochemical properties (PCPs) obtained by means of an optimal feature selection algorithm. Then, molecular dynamics simulations were performed for validating the knowledge discovered by analysis of the selected PCPs.ResultsThe RSA predictors had the mean absolute error of 14.11% and a correlation coefficient of 0.69, better than the existing predictors. The hydrophilic-residue predictors preferred PCPs of buried amino acid residues to PCPs of exposed ones as prediction features. A hydrophobic spine composed of exposed hydrophobic residues of an α-helix was discovered by analyzing the PCPs of RSA predictors corresponding to hydrophobic residues. For example, the results of a molecular dynamics simulation of wild-type sequences and their mutants showed that proteins 1MOF and 2WRP_H16I (Protein Data Bank IDs), which have a perfectly hydrophobic spine, have more stable structures than 1MOF_I54D and 2WRP do (which do not have a perfectly hydrophobic spine).ConclusionsWe identified informative PCPs to design high-performance RSA predictors and to analyze these PCPs for identification of novel protein folding characteristics. A hydrophobic spine in a protein can help to stabilize exposed α-helices.

【 授权许可】

CC BY   
© The Author(s). 2016

【 图 表 】

Fig. 2

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