Simulation of Protein Folding Process
| Project/Area Number |
15300101
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioinformatics/Life informatics
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| Research Institution | Ochanomizu University (2005)
Nagahama Institute of Bio-Science and Technology (2003-2004) |
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Principal Investigator |
GO Mitiko Ochanomizu University, President, 学長 (70037290)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Ken-ichi Nagahama Institute of Bio-Science and Technology, Faculty of Bio-Science, Associate Professor, バイオサイエンス学部, 助教授 (20322737)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2005: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2004: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Protein folding / Module / Molecular dynamics simulation / Protein G / Barnase / Hierarchical formation / Hydrophobic core / Secondary structure / AMBER / protein G / 力場パラメタ |
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| Research Abstract |
Despite huge degree of conformational freedom, protein can fold into its specific native structure within a physiological time scale. To elucidate its mechanism, we performed heat-induced unfolding simulations of barnase and protein G.
For barnase, performing ten runs of molecular dynamics simulations at 498 K, we characterized a common feature on unfolding processes. Hydrophobic cores and secondary structures seen in the native state were gradually disrupted until they were all eventually lost except some very local regions kept their native-like conformations. This is consistent with known experimental results. Our novel finding is that the native hierarchical structure composed of compact substructures, called modules, were well sustained in such extensive unfolded states in a sense that segmental regions corresponding to the native modules kept relatively compact conformations despite the whole protein structure largely inflated. Furthermore, hydrophobic interactions between both te
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rmini of modules were retained with high probability, which would be a main factor to stabilize module structures.
For protein G, although early simulation results were inconsistent with known experiments, reconsidering simulation conditions revealed that the problem was likely ascribed to lower dielectric constants at higher simulation temperatures. And then, by using a less stable mutant or reduced-charge conditions, we obtained simulation results consistent with the experiments. Analyzing these simulation data, we found a similar unfolding feature to that of barnase, that is, native-like hierarchical structures composed of relatively compact substructures had a tendency to be sustained despite large disruption of hydrophobic cores and secondary structures occurred as unfolding proceeded.
In conclusion, formation of module structures in an early stage of folding process could be a key to solve the folding problem, that is, a key to reduce conformational space to be searched for the native structure. Less
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Report
(4 results)
Research Products
(4 results)
