Development of frontier molecular design and reaction control method based on integrated free energy profile analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05375
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 32010:Fundamental physical chemistry-related
• Research Institution: Osaka Prefecture University
• Principal Investigator: ASADA TOSHIO 大阪府立大学, 理学(系)研究科(研究院), 教授 (10285314)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 分子分極 / 原子分極 / 自由エネルギー / 反応経路 / カルバペネマーゼ / メロペネム

Outline of Final Research Achievements

We have elucidated the degradation reaction mechanism of meropenem, which is a carbapenem antibotic expected to be the last trump card against multidrug-resistant bacteria, by the carbapenemase produced by the resistant bacteria using the free energy gradients and a reaction-path optimization methods. The effects of amino acid residues constituting the enzyme on the reaction free energy barrier was quantitatively clarified. While it is not possible to modify the structure of the enzyme produced by the bacteria, we have succeeded in proposing a guideline for drug design by considering the electric field from each aminoacid in the enzyme as an external electric field.

Free Research Field

理論計算科学

Academic Significance and Societal Importance of the Research Achievements

独自の反応経路最適化法と各アミノ酸からの反応自由エネルギー障壁への寄与解析により、全アミノ酸残基からの定量的な影響を解明することに成功した。新しい多剤耐性菌は今後も次々と未知の細菌によって生み出させることが想定される。しかしながら、本研究手法の汎用性の確立によって任意の酵素による抗生剤分解反応を阻止するような分子設計に直結し、経済的にも社会的にも大変有意義なものとなったと結論づけることができる。