Free-energy function based on an all-atom model for proteins

Takashi Yoshidome, Koji Oda, Yuichi Harano, Roland Roth, Yuji Sugita, Mitsunori Ikeguchi, Masahiro Kinoshita

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)950-961
Number of pages12
JournalProteins: Structure, Function and Bioinformatics
Issue number4
Publication statusPublished - 2009


  • Decoy recognition
  • Dehydration
  • Hydration entropy
  • Molecular liquid
  • Morphometric approach
  • Protein folding
  • Statistical mechanics
  • Structure prediction


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