Development of super-resolution structure analysis techniques for bio-macromolecules based on a quantum chemical calculation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K05397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical chemistry
• Research Institution: Hoshi University (2016-2017); Nihon University (2015)
• Principal Investigator: Fukuzawa Kaori (秋葉薫) 星薬科大学, 薬学部, 准教授 (50718244)
• Co-Investigator(Renkei-kenkyūsha): HONMA Teruki 理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (10466039) ; TANAKA Shigenori 神戸大学, システム情報学研究科, 教授 (10379480) ; TSURUTA Hiroki 神戸大学, 学術・産業イノベーション創造本部, 准教授 (20346282)
• Research Collaborator: WATANABE Chiduru 理化学研究所, ライフサイエンス技術基盤研究センター, 研究員
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: フラグメント分子軌道法 / 創薬分子設計 / 計算構造生物学 / 電子密度解析 / 構造精密化 / 超分解能解析 / 量子化学計算 / タンパク質

Outline of Final Research Achievements

In this study, we are developing a new precise structure determination method of protein - ligand complex by using X-ray crystal structure analysis and quantum chemical calculation. Based on the fragment molecular orbital method, we attempted to use the energy calculation, structure optimization, interaction analysis, and electron density analysis to substantially increase the resolution of structural analysis by experiment. t was shown that quantum chemical calculations are quite useful in predicting high-precision activity of Pim 1 kinase inhibitors, hydration of anti-influenza drugs, prediction of high-resolution structures from low-resolution crystal structures of estrogen receptors.

Free Research Field

量子化学計算を用いた、計算生命科学、計算構造生物学および創薬等分子設計への応用