2012 Fiscal Year Final Research Report
Development of molecular simulation algorithms for enhancing structural fluctuations and for accurate free -energy calculations
| Project Area | Molecular Science of Fluctuations toward Biological Functions |
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| Project/Area Number |
20107002
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Nagoya University |
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Principal Investigator |
OKAMOTO Yuko 名古屋大学, 理学研究科, 教授 (70185487)
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| Project Period (FY) |
2008 – 2012
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| Keywords | 生体系 / 蛋白質 / 分子シミュレーション / 拡張アンサンブル法 / 自由エネルギー |
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| Research Abstract |
Several generalized-ensemble algorithms that enhance structural fluctuations and that allow accurate free-energy calculations were developed. In particular, a general formalism for multidimensional/multivariable generalized-ensemble algorithms was obtained. Direct folding of villin headpiece from a fully extended initial conformation into the native one was achieved by a generalized-ensemble simulation. The conformations of ligands in the ligand-protein complexes were predicted by generalized-ensemble simulations, and they were shown to be in good agreement with those of the X-ray experiments. This presents a new method for drug design. A generalized-ensemble simulation for isobaric-isothermal ensemble has been performed for ubiquitin in aqueous solution, and the results of high pressure NMR experiments by Kitahara and Akasaka that the chemical shifts of the 70th residue greatly changes as pressure changes were reproduced. These results imply that generalized-ensemble algorithms are effective in quantitative predictions in simulations of all-atom models. Great future development is expected.
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