Development of novel free energy change prediction method independent of entropy change

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K06615
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Kindai University
• Principal Investigator: Kawashita Norihito 近畿大学, 理工学部, 准教授 (00423111)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 分子設計 / エントロピー / 自由エネルギー / フラグメント分子軌道法 / ドッキングシミュレーション / 機械学習

Outline of Final Research Achievements

The development of drugs requires an enormous amount of cost and time, and there is a strong need to improve the efficiency of drug development. In this study, we devised a computer-based method for predicting the free energy change of a compound (one of the indicators of how strongly it interacts with its target) and verified its applicability in order to improve its efficiency. In this study, HIV protease and other complexes were examined. First, we compared the calculated values obtained by computer with known experimental varues to examine the applicability of this prediction method. The results showed the applicability of the method by classifying compounds according to appropriate criteria. Next, we constructed a prediction equation from the calculation results, and were able to predict the free energy change within a reasonable error range.

Free Research Field

計算化学、分子設計学

Academic Significance and Societal Importance of the Research Achievements

化合物がどの程度強く薬の標的と相互作用するかの指標の1つである自由エネルギー変化の予測は非常に困難であることがわかっている。本手法は、これまでの手法とは異なり、計算が困難な情報を計算することなく自由エネルギー変化を予測できることが特徴である。さらなる利点として、一度良い予測式が得られれば、大幅な実験データの増加が得られない限り、同じ系においてはこれを引き続き使用して予測できることにある。それゆえ、本法は非常に強力な阻害剤探索ツールとなる可能性を秘めている。