O08_06
Progress of data collection in FMO database and efforts to evaluate structural qualities of biological macromolecules using quantum chemical interaction energy analysis
Chiduru WATANABE *1, Kikuko KAMISAKA1, Chie TAKEMOTO1, Norihiko TANI1, Tomohiro SATO1, Toru SENGOKU2, Yoshio OKIYAMA3, Teruki HONMA1
1Center for Biosystems Dynamics Research, RIKEN
2Graduate School of Medicine, Yokohama City University
3Graduate School of System Informatics, Kobe University
( * E-mail: chiduru.watanabe@riken.jp)
Elucidating biomolecular interactions such as protein–ligand, protein–protein, and nucleic acid interactions is vital information for drug discovery and structural biology. Our group has been focusing on quantum mechanics (QM), which incorporates the effects of donating and withdrawing electrons and charge transfer and can appropriately deal with the CH/π and π–π interactions. Fragment molecular orbital (FMO) method [1] enables us to efficiently perform ab initio QM calculations for large biomolecules. The benefit of this fragmentation scheme is the availability of interfragment interaction energy (IFIE) and pair interaction energy decomposition analysis (PIEDA).
Since 2014, our group has been developing an FMO database of quantum chemical calculations of biological macromolecules [2]. In constructing the database, we continue developing and improving automated FMO calculation protocols for its data collection [3]. We have collected FMO calculation data focusing on apoproteins, kinases, nuclear receptors, antigen–antibodies, COVID-19-related proteins, and others. This year, we are collecting data considering drug discovery modalities and AI, focusing on antibodies, nucleic acids, and AlphaFold structures. In this presentation, we will introduce the status of the collection of these FMO data, IFIE/PIEDA analysis for various interactions meaningful for structural folding and molecular recognition, and quality evaluation efforts for FMO calculations and their initial structures of biological macromolecules.
Acknowledgment
The authors thank Mr. Yuya Seki of TechnoPro R&D Company for FMO calculation support. This research was done as a part of activities of the FMO Drug Design Consortium (URL: https://fmodd.jp). This research was partially supported by 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 JP24ama121030. The authors acknowledge JSPS KAKENHI Grant No. 23K18192. The results of FMO calculations were obtained using the Fugaku (project IDs: hp240114 and ra000017) and the Hokusai (project ID: RB230116).
References
[1] Kitaura, K. et al., Chem. Phys. Lett. 1999, 313, 701–706.
[2] Takaya, D. et al., J. Chem. Inf. Model. 2021, 61, 777–794.
[3] C. Watanab et al., CBI J. 2019, 19, 5–18.