title: Free-energy function for discriminating the native fold of a protein from misfolded decoys.
abstract: In this study, free-energy function (FEF) for discriminating the native fold of a protein from misfolded decoys was investigated. It is a physics-based function using an all-atom model, which comprises the hydration entropy (HE) and the total dehydration penalty (TDP). The HE is calculated using a hybrid of a statistical-mechanical theory applied to a molecular model for water and the morphometric approach. The energetic component is suitably taken into account in a simple manner as the TDP. On the basis of the results from a careful test of the FEF, which have been performed for 118 proteins in representative decoy sets, we show that its performance is distinctly superior to that of any other function. The FEF varies largely from model to model for the candidate models for the native structure (NS) obtained from nuclear magnetic resonance experiments, but we can find models or a model for which the FEF becomes lower than for any of the decoy structures. A decoy set is not suited to the test of a free-energy or potential function in cases where a protein isolated from a protein complex is considered and the structure in the complex is used as the model NS of the isolated protein without any change or where portions of the terminus sides of a protein are removed and the percentage of the secondary structures lost due to the removal is significantly high. As these findings are made possible, we can assume that our FEF precisely captures the features of the true NS.
authors.affiliation: Graduate School of Energy Science, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshidome
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Harano
authors.forename: Roland
authors.initials: R
authors.lastname: Roth
authors.forename: Hiraku
authors.initials: H
authors.lastname: Oshima
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D008956:Models, Chemical; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011506:Proteins