2013 Fiscal Year Final Research Report
Prediction of 3D Structure of Drug Target GPCR Using Evolutionary Computation
| Project/Area Number |
23500376
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bioinformatics/Life informatics
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| Research Institution | Yamaguchi University |
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Principal Investigator |
ISHINO Yoko 山口大学, 大学院技術経営研究科, 准教授 (90373266)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 生命分子計算 / 進化計算 / バイオインフォマティクス |
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| Research Abstract |
G-Protein coupled receptors (GPCRs) are one of the most important drug target proteins today. However, the 3D structures of GPCRs have not yet been determined by X-ray crystallography, except a few proteins, because GPCRs are difficult to crystallize. In addition, due to the huge structural fluctuation of GPCRs, there is a limitation to computationally predict GPCR's accurate conformation.
This study developed a new method for modeling GPCR thermal fluctuations, where conformation changes of the proteins are modeled by combining fluctuations on multiple time scales. This study proposed a novel method which predicts a best 3D structure of a GPCR from a variety of fluctuating candidate structures, by using the evolutionary computation including receptor-ligand docking simulations. The method was validated using human leukotriene B4 receptor BLT1 as a sample GPCR.
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