最先端研究セミナー

講演者：　 石川 岳志（鹿児島大学工学部 先進工学科 化学生命工学プログラム 生命計算化学研究室）

演題：　Drug Discovery Using Computational Chemistry: Method Development and Applications

日時： 2023年10月11日（水）12:00- 13:00

Abstract:

Computational chemistry is a research field in which various chemical phenomena are understood and predicted by solving the physical equations that molecules, atoms, or electrons obey. In our laboratory, we are conducting a variety of research in the life sciences, including drug discovery, based on computational chemistry. In this lecture, I will give an overview of computer simulations in life science research and then talk about two topics of our recent research.

One of them is the development of anti-prion compounds using computational chemistry. Prion disease is a fatal disease caused by the structural change of prion protein from the cellular form (PrP^C) to the abnormal scrapie form (PrP^SC). We have discovered several anti-prion compounds, i.e., the GN8 series at Gifu University [1], the NPR series at Nagasaki University [2], and the NPRS series at Kagoshima University. In these drug discoveries, methods of computational chemistry, including docking simulation, molecular dynamics (MD) simulation, and quantum chemical simulation, were efficiently used. My lecture will show how computational chemistry was used to develop these anti-prion compounds. In addition, we will present a new computational method for drug discovery based on MD simulation, which has been developed in our laboratory in recent years.

Another topic is our novel method to analyze protein-protein interaction (PPI). PPI has significant roles in various biological processes and, consequently, attracts much attention as a prospective therapeutic target. Adequate understanding of PPI is also essential for the logical design of antibody drugs, whose demand has been rapidly increasing. Recently, we proposed a method called “visualization of the interfacial electrostatic complementarity (VIINEC)” [3,4,5] based on the fragment molecular orbital (FMO) method, which is a quantum chemical approach for large molecules like proteins. In my talk, methodological aspects of the VIINEC are explained. After that, the potential of VIINEC is demonstrated using some applications.

References:

[1] K. Yamaguchi, et al, Nat. Biomed. Eng., 3 (2019) 206-219

[2] D. Ishibashi*, et al, EBioMedicine, 9 (2016) 238-249

[3] H. Ozono, et al, J. Chem. Theory Comput. 17 (2021) 5600

[4] T. Ishikawa*, et al, J. Phys. Chem. Lett., 12 (2021) 11267

[5] H. Ozono, et al, J. Phys. Chem. B, 126 (2022) 8415