Study on the mechanism of docking of small molecules to proteins by generalized-ensemble algorithms

2017 Fiscal Year Final Research Report

• Project/Area Number: 25247071
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological physics/Chemical physics/Soft matter physics
• Research Institution: Nagoya University
• Principal Investigator: OKAMOTO Yuko 名古屋大学, 理学研究科, 教授 (70185487)
• Project Period (FY): 2013-04-01 – 2018-03-31
• 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 / 自由エネルギー計算 / 量子効果

Outline of Final Research Achievements

We have modified our own method for docking of a ligand to a protein based on one of the generalized-ensemble algorithms, i.e., replica-exchange umbrella sampling (REUS), in two steps, and succeeded in developing a new method for calculating the binding free energy of a ligand to a protein. By applying a docking simulation method based on rEUS, we succeeded in obtaining the isozyme selectivity of histon
deacetylase inhibitor in agreement with experiments. We also showed that this selectivity comes from the difference in the three-dimensional structures of hydrophobic residues that surround the ligand.

Free Research Field

生物物理学、計算化学、計算物理学