A scoring function based on solvation thermodynamics for protein structure prediction
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- Du Shiqiao
- Center for Biological Resources and Informatics, Tokyo Institute of Technology
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- Harano Yuichi
- Institute for Protein Research, Osaka University
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- Sakurai Minoru
- Center for Biological Resources and Informatics, Tokyo Institute of Technology
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- Kinoshita Masahiro
- Institute of Advanced Energy, Kyoto University
書誌事項
- 公開日
- 2012
- 資源種別
- journal article
- DOI
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- 10.2142/biophysics.8.127
- 公開者
- 日本生物物理学会
説明
We predict protein structure using our recently developed free energy function for describing protein stability, which is focused on solvation thermodynamics. The function is combined with the current most reliable sampling methods, i.e., fragment assembly (FA) and comparative modeling (CM). The prediction is tested using 11 small proteins for which high-resolution crystal structures are available. For 8 of these proteins, sequence similarities are found in the database, and the prediction is performed with CM. Fairly accurate models with average C<symbol>a</symbol> root mean square deviation (RMSD) ~ 2.0 Å are successfully obtained for all cases. For the rest of the target proteins, we perform the prediction following FA protocols. For 2 cases, we obtain predicted models with an RMSD ~ 3.0 Å as the best-scored structures. For the other case, the RMSD remains larger than 7 Å. For all the 11 target proteins, our scoring function identifies the experimentally determined native structure as the best structure. Starting from the predicted structure, replica exchange molecular dynamics is performed to further refine the structures. However, we are unable to improve its RMSD toward the experimental structure. The exhaustive sampling by coarse-grained normal mode analysis around the native structures reveals that our function has a linear correlation with RMSDs < 3.0 Å. These results suggest that the function is quite reliable for the protein structure prediction while the sampling method remains one of the major limiting factors in it. The aspects through which the methodology could further be improved are discussed.<br>
収録刊行物
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- BIOPHYSICS
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BIOPHYSICS 8 (0), 127-138, 2012
日本生物物理学会
