2015 Fiscal Year Final Research Report
Development and its Application of Novel Drug Design based on the first-principles calculation
| Project/Area Number |
25460157
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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 |
Drug development chemistry
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| Research Institution | Rikkyo University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | in silico創薬 / 理論創薬 / 全電子計算 / フラグメント分子軌道法 / 核内受容体 |
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| Outline of Final Research Achievements |
Novel Drug Design procedure combined the first-principles calculation using ab initio fragment molecular orbital (FMO) method with bioinfomatics were established. Correlated FMO calculations can evaluate correctly not only hydrophilic (electrostatic) but also hydrohobic (van der Waals dispersion) interactions between amino acid residues in target protein and drug candidates. New anti-influenza virus inhibitors were rationally developed by the interfragment interaction energy (IFIE) analysis based on the FMO scheme. And antidiabetic compounds without side effect as partial agonists for nuclear receptors such as vitamin D receptor (VDR), retinoid X receptor (RXR), and steroid X receptor (SXR) were also developed and synthetized. The functional domain in the target protein was explored by the sequence alignment analysis, and key residues between these candidates and target protein were determined by the FMO-IFIE analysis.
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| Free Research Field |
創薬化学
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