Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1368-z) contains supplementary material, which is available to authorized users.
Highlights
Most of hydrophilic and hydrophobic residues are thought to be exposed and buried in proteins, respectively
The informative physicochemical properties (PCPs) were analyzed. These PCPs indicated that a hydrophobic spine can help to stabilize a protein structure
To ensure that the solvent distribution was kept at the minimum energy, the atoms of proteins were first fixed and subjected to 50,000 iterations of the steepest descent energy minimization, and 200-ps molecular dynamics [22] simulations were performed for solvation
Summary
Most 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. Hikijata et al [3] predicted three-dimensional (3D) structures of proteins using alignment results and solvent accessibility of residues. Kumar and Bansal [6] analyzed α-helices in globular proteins and suggested that Ncap is mostly composed of Ser, Asp, Thr, Asn, Gly, and Pro. Pascarella et al [7] and Bartlett et al [8] used 3D structure information to study solvent accessibility of residues and characteristics of catalytic sites, respectively. Shirota et al [9] estimated the surface-to-volume ratio of residues to examine the sequence-structure relation
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