著者

Kazunori Miwa Yan Guo Masayuki Hata Yoshinori Hirano Norio Yamamoto Tyuji Hoshino

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.12, pp.897-905, 2023-12-01 (Released:2023-12-01)

参考文献数

40

---

Virtual screening with high-performance computers is a powerful and cost-effective technique in drug discovery. A chemical database is searched to find candidate compounds firmly bound to a target protein, judging from the binding poses and/or binding scores. The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infectious disease has spread worldwide for the last three years, causing severe slumps in economic and social activities. SARS-Cov-2 has two viral proteases: 3-chymotrypsin-like (3CL) and papain-like (PL) protease. While approved drugs have already been released for the 3CL protease, no approved agent is available for PL protease. In this work, we carried out in silico screening for the PL protease inhibitors, combining docking simulation and molecular mechanics calculation. Docking simulations were applied to 8,820 molecules in a chemical database of approved and investigational compounds. Based on the binding poses generated by the docking simulations, molecular mechanics calculations were performed to optimize the binding structures and to obtain the binding scores. Based on the binding scores, 57 compounds were selected for in vitro assay of the inhibitory activity. Five inhibitory compounds were identified from the in vitro measurement. The predicted binding structures of the identified five compounds were examined, and the significant interaction between the individual compound and the protease catalytic site was clarified. This work demonstrates that computational virtual screening by combining docking simulation with molecular mechanics calculation is effective for searching candidate compounds in drug discovery.

著者

Kazunori Miwa Yan Guo Masayuki Hata Norio Yamamoto Tyuji Hoshino

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.5, pp.360-367, 2023-05-01 (Released:2023-05-01)

参考文献数

39

被引用文献数

3

---

Computational screening is one of the fundamental techniques in drug discovery. Each compound in a chemical database is bound to the target protein in virtual, and candidate compounds are selected from the binding scores. In this work, we carried out combinational computation of docking simulation to generate binding poses and molecular mechanics calculation to estimate binding scores. The coronavirus infectious disease has spread worldwide, and effective chemotherapy is strongly required. The viral 3-chymotrypsin-like (3CL) protease is a good target of low molecular-weight inhibitors. Hence, computational screening was performed to search for inhibitory compounds acting on the 3CL protease. As a preliminary assessment of the performance of this approach, we used 51 compounds for which inhibitory activity had already been confirmed. Docking simulations and molecular mechanics calculations were performed to evaluate binding scores. The preliminary evaluation suggested that our approach successfully selected the inhibitory compounds identified by the experiments. The same approach was applied to 8820 compounds in a database consisting of approved and investigational chemicals. Hence, docking simulations, molecular mechanics calculations, and re-evaluation of binding scores including solvation effects were performed, and the top 200 poses were selected as candidates for experimental assays. Consequently, 25 compounds were chosen for in vitro measurement of the enzymatic inhibitory activity. From the enzymatic assay, 5 compounds were identified to have inhibitory activities against the 3CL protease. The present work demonstrated the feasibility of a combination of docking simulation and molecular mechanics calculation for practical use in computational virtual screening.

著者

田口 聡志 上枝 正幸 三輪 一統 Satoshi Taguchi Masayuki Ueeda Kazunori Miwa タグチ サトシ ウエエダ マサユキ ミワ カズノリ

出版者

同志社大学商学会

雑誌

同志社商学 (ISSN:03872858)

巻号頁・発行日

vol.67, no.4, pp.469-495, 2016-03

---

瀧田輝己教授退職記念号

著者

Satoshi Taguchi Masayuki Ueeda Kazunori Miwa Satoshi Mizutani

出版者

Research Institute for Economics & Business Administration - Kobe University

雑誌

The Japanese Accounting Review (ISSN:21854785)

巻号頁・発行日

vol.3, no.2013, pp.103-120, 2013-12-26 (Released:2014-02-13)

参考文献数

24

---

This paper examines whether the movement toward convergence of the International Financial Reporting Standards (IFRS) has ended. The methodology for this research is based on comparative institutional analysis and experimental game theory. In addition,we adopt a 3×3 coordination game because an essential factor of global accounting convergence is the coordination of accounting standards. The results confirm the termination of a movement toward the convergence of IFRS. Namely, our experiments indicate that global accounting convergence toward IFRS may not be successful. This is because some “egoist” countries maintain their initial systems and do not enter long term cooperation.