title: Free-energy function based on an all-atom model for proteins.
abstract: We have developed a free-energy function based on an all-atom model for proteins. It comprises two components, the hydration entropy (HE) and the total dehydration penalty (TDP). Upon a transition to a more compact structure, the number of accessible configurations arising from the translational displacement of water molecules in the system increases, leading to a water-entropy gain. To fully account for this effect, the HE is calculated using a statistical-mechanical theory applied to a molecular model for water. The TDP corresponds to the sum of the hydration energy and the protein intramolecular energy when a fully extended structure, which possesses the maximum number of hydrogen bonds with water molecules and no intramolecular hydrogen bonds, is chosen as the standard one. When a donor and an acceptor (e.g., N and O, respectively) are buried in the interior after the break of hydrogen bonds with water molecules, if they form an intramolecular hydrogen bond, no penalty is imposed. When a donor or an acceptor is buried with no intramolecular hydrogen bond formed, an energetic penalty is imposed. We examine all the donors and acceptors for backbone-backbone, backbone-side chain, and side chain-side chain intramolecular hydrogen bonds and calculate the TDP. Our free-energy function has been tested for three different decoy sets. It is better than any other physics-based or knowledge-based potential function in terms of the accuracy in discriminating the native fold from misfolded decoys and the achievement of high Z-scores.
authors.affiliation: Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshidome
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Harano
authors.forename: Roland
authors.initials: R
authors.lastname: Roth
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: D003198:Computer Simulation; D019277:Entropy; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D007477:Ions; D011506:Proteins; D014867:Water