title: Determination of protein folding kinetic types using sequence and predicted secondary structure and solvent accessibility.
abstract: Proteins fold through a two-state (TS), with no visible intermediates, or a multi-state (MS), via at least one intermediate, process. We analyze sequence-derived factors that determine folding types by introducing a novel sequence-based folding type predictor called FOKIT. This method implements a logistic regression model with six input features which hybridize information concerning amino acid composition and predicted secondary structure and solvent accessibility. FOKIT provides predictions with average Matthews correlation coefficient (MCC) between 0.58 and 0.91 measured using out-of-sample tests on four benchmark datasets. These results are shown to be competitive or better than results of four modern predictors. We also show that FOKIT outperforms these methods when predicting chains that share low similarity with the chains used to build the model, which is an important advantage given the limited number of annotated chains. We demonstrate that inclusion of solvent accessibility helps in discrimination of the folding kinetic types and that three of the features constitute statistically significant markers that differentiate TS and MS folders. We found that the increased content of exposed Trp and buried Leu are indicative of the MS folding, which implies that the exposure/burial of certain hydrophobic residues may play important role in the formation of the folding intermediates. Our conclusions are supported by two case studies.
authors.affiliation: School of Computer Science and Information Engineering, Zhejiang Gongshang University, Hangzhou, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Tuo
authors.initials: T
authors.lastname: Zhang
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Gao
authors.forename: Jishou
authors.initials: J
authors.lastname: Ruan
authors.forename: Shiyi
authors.initials: S
authors.lastname: Shen
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kurgan
mesh_terms: D030562:Databases, Protein; D007700:Kinetics; D016015:Logistic Models; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000032:analysis*; D020539:Sequence Analysis, Protein; D012997:Solvents / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents