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Taking Water into Account with the Fragment Molecular Orbital Method

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Quantum Mechanics in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2114))

Abstract

This chapter describes the current status of development of the fragment molecular orbital (FMO) method for analyzing the electronic state and intermolecular interactions of biomolecular systems in solvent. The orbital energies and the inter-fragment interaction energies (IFIEs) for a specific molecular structure can be obtained directly by performing FMO calculations by exposing water molecules and counterions around biomolecular systems. Then, it is necessary to pay attention to the thickness of the water shell surrounding the biomolecules. The single-point calculation for snapshots from MD trajectory does not incorporate the effects of temperature and configurational fluctuation, but the SCIFIE (statistically corrected IFIE) method is proposed as a many-body correlated method that partially compensates for this deficiency. Furthermore, implicit continuous dielectric models have been developed as effective approaches to incorporating the screening effect of the solvent in thermal equilibrium, and we illustrate their usefulness for theoretical evaluation of IFIEs and ligand-binding free energy on the basis of the FMO-PBSA (Poisson–Boltzmann surface area) method and other computational methods.

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Acknowledgments

This work was supported by JSPS KAKENHI Grant Numbers 17H06353 and 18K03825.

Author information

Authors and Affiliations

  1. Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Kanagawa, Japan

    Yoshio Okiyama

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

    Kaori Fukuzawa

  3. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan

    Yuto Komeiji

  4. Department of Computational Science, Graduate School of System Informatics, Kobe University, Kobe, Japan

    Shigenori Tanaka

Authors
  1. Yoshio Okiyama
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  2. Kaori Fukuzawa
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  3. Yuto Komeiji
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  4. Shigenori Tanaka
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Corresponding author

Correspondence to Shigenori Tanaka .

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Editors and Affiliations

  1. Evotec (UK) Ltd., Abingdon, Oxfordshire, UK

    Alexander Heifetz

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Okiyama, Y., Fukuzawa, K., Komeiji, Y., Tanaka, S. (2020). Taking Water into Account with the Fragment Molecular Orbital Method. In: Heifetz, A. (eds) Quantum Mechanics in Drug Discovery. Methods in Molecular Biology, vol 2114. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0282-9_7

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  • DOI: https://doi.org/10.1007/978-1-0716-0282-9_7

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0281-2

  • Online ISBN: 978-1-0716-0282-9

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