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FMO Drug Design Consortium

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Recent Advances of the Fragment Molecular Orbital Method

Abstract

Drug discovery is one of the most important applications of the fragment molecular orbital (FMO) method. By using the FMO calculation, it is possible to determine the binding properties between a drug candidate compound and a target protein, predict the binding activity, and begin to produce a rational design for the new drug compound. The FMO drug discovery consortium is an industry–academia–government cooperation group, which is conducting various studies with the aim of developing the FMO method as a practical in silico drug discovery technology. In this chapter, we introduce the status of the research conducted by four working groups (WGs) focusing on drug target proteins (the kinase, protease, nuclear receptor, and protein–protein interaction WGs) and two WGs focusing on methodology (one WG responsible for developing drug discovery methods and databases and one collaboration with the molecular dynamics-based KBDD, i.e., K supercomputer-based drug discovery, consortium). We also discuss the current state and challenges of FMO-based drug discovery.

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Acknowledgments

The authors thank Prof. Tatsuya Takagi, Dr. Midori Kamimura, and Dr. Tomonaga Ozawa for managing FMODD and for conducting many research discussions. The authors also thank Dr. Chiduru Watanabe and Dr. Yoshio Okiyama for FMO calculations and assistance in the preparation of figures. The results of FMO calculations were obtained using the HPCI system including the K computer at RIKEN, TSUBAME 3.0 at the Tokyo Institute of Technology, and FX100 at Nagoya University (project IDs: hp150160, hp160103, hp170183, hp180147, hp190119, and hp190133). Prof. Yuji Mochizuki supported the use of the ABINIT-MP program on HPCI. PIEDA calculations were conducted using the MIZUHO/BioStation software package. This research was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP20am0101113. The docking poses from Chapter 8.6 were provided by Dr. Mitsugu Araki and coworkers from the KBDD project by the Biogrid pharma consortium. K computer project IDs: hp150025, hp160010, and hp170036. The authors would like to thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo, 142-8501, Japan

    Kaori Fukuzawa

  2. Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11 AobaAoba-ku, Aramaki, 980-8579, Japan

    Kaori Fukuzawa

  3. Graduate School of System Informatics, Department of Computational Science, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, 657-8501, Japan

    Shigenori Tanaka

  4. Graduate School of Engineering, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama, 700-0005, Japan

    Yoichiro Yagi

  5. Department of Computer Science and Engineering, Toyohashi University of Technology, 1-1 Hibarigaoka Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan

    Noriyuki Kurita

  6. Faculty of Science and Engineering, Kindai University, 3-4-1 Kowakae, Higashiosaka, Osaka, 577-8502, Japan

    Norihito Kawashita

  7. Pharmaceuticals Research Center, Laboratory for Medicinal Chemistry, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka, 410-2321, Japan

    Kenichiro Takaba

  8. RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan

    Teruki Honma

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  1. Kaori Fukuzawa
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Correspondence to Kaori Fukuzawa .

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Editors and Affiliations

  1. Department of Chemistry, Faculty of Science, Rikkyo University, Tokyo, Japan

    Yuji Mochizuki

  2. Graduate School of System Informatics, Kobe University, Kobe, Japan

    Shigenori Tanaka

  3. School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan

    Kaori Fukuzawa

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Fukuzawa, K. et al. (2021). FMO Drug Design Consortium. In: Mochizuki, Y., Tanaka, S., Fukuzawa, K. (eds) Recent Advances of the Fragment Molecular Orbital Method. Springer, Singapore. https://doi.org/10.1007/978-981-15-9235-5_8

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