Development of a novel dispersion energy estimation method for reliable in silico drug discovery

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: Nagasaki International University
• Principal Investigator: Yoshida Tatsusada 長崎国際大学, 薬学部, 講師 (80527557)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 分散力エネルギー / イン・シリコ創薬 / 分子軌道法 / 分子間相互作用 / レクチン

Outline of Final Research Achievements

This research purpose is to continuously develop and improve a simple but effective approach for the evaluation of dispersion energies, to gain a detailed understanding of inter- and intra-molecular interactions involving biomolecules at the atomic and electronic level, and to apply it to in silico screening with higher accuracy and less computational time.
Accuracy verification using non-covalent interaction complexes showed performance comparable to or superior to that of computationally expensive methods based on electron correlation theory. In binding interaction analyses of several protein-ligand complex systems, this approach could reproduce observed binding free-energy changes nicely, demonstrating its usefulness in ligand screening.

Free Research Field

計算科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、弱いが故にその評価が困難であった分散力エネルギーを簡便かつ精確に見積もることができるようになれば、膨大数の医薬品候補化合物を高速に扱うために信頼性の低い古典力場計算やドッキング計算が主流であったインシリコ・スクリーニングの信頼度の向上や分散力を自在に制御した精密な医薬品分子設計、人工変異タンパク質のデザイン等への応用に繋がる。また、結合親和性が弱いため、正確な認識メカニズムの理解が困難である糖鎖・レクチン複合体の相互作用解析に基づく網羅的な糖鎖プロファイリングへの展開等が考えられる。