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Biomolecular Simulations pp 155–177Cite as

Replica-Exchange Methods for Biomolecular Simulations

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2022))

Abstract

In this study, a replica-exchange method was developed to overcome conformational sampling difficulties in computer simulations of spin glass or other systems with rugged free-energy landscapes. This method was then applied to the protein-folding problem in combination with molecular dynamics (MD) simulation. Owing to its simplicity and sampling efficiency, the replica-exchange method has been applied to many other biological problems and has been continuously improved. The method has often been combined with other sampling techniques, such as umbrella sampling, free-energy perturbation, metadynamics, and Gaussian accelerated MD (GaMD). In this chapter, we first summarize the original replica-exchange molecular dynamics (REMD) method and discuss how new algorithms related to the original method are implemented to add new features. Heterogeneous and flexible structures of an N-glycan in a solution are simulated as an example of applications by REMD, replica exchange with solute tempering, and GaMD. The sampling efficiency of these methods on the N-glycan system and the convergence of the free-energy changes are compared. REMD simulation protocols and trajectory analysis using the GENESIS software are provided to facilitate the practical use of advanced simulation methods.

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Acknowledgements

Y.S. thanks especially Yuko Okamoto for the collaboration and guidance to develop T-REMD, MREM, REUS, and MUCAREM at the Institute for Molecular Science. We are grateful to the young scientists who have worked with us in RIKEN for the development of replica-exchange methods and the applications (Naoyuki Miyashita, Takaharu Mori, Raimondas Galvelis, Daisuke Matsuoka, Ai Niitsu, George Pantelopulos). Computer resources were provided by HOKUSAI GreatWave in RIKEN Advanced Center for Computing and Communication and K computer in RIKEN Center for Computational Science through the HPCI System Research project (Project IDs ra000009, hp140169, hp150108, hp150270, hp160207, hp170254, and hp170115). This research has been funded by strategic programs for innovation research: “Computational life science and application in drug discovery and medical development,” “Novel measurement techniques for visualizing live protein molecules at work” (Grant No. 26119006), JST CREST on “Structural Life Science and Advanced Core Technologies for Innovative Life Science Research” (Grant No. JPMJCR13M3), RIKEN pioneering research projects on “Dynamics Structural Biology” and “Integrated Lipidology” (to Y.S.), and MEXT/JSPS KAKENHI Grant Numbers 25330358 and 16K00415 (to S.R.).

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Authors and Affiliations

  1. Theoretical Molecular Science Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan

    Yuji Sugita

  2. Computational Biophysics Research Team, RIKEN Center for Computational Science, Kobe, Japan

    Yuji Sugita & Motoshi Kamiya

  3. Laboratory for Biomolecular Function Simulation, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan

    Yuji Sugita, Hiraku Oshima & Suyong Re

Authors
  1. Yuji Sugita
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  2. Motoshi Kamiya
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  3. Hiraku Oshima
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  4. Suyong Re
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Corresponding author

Correspondence to Yuji Sugita .

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Editors and Affiliations

  1. Structural Bioinformatics Unit, Institut Pasteur, CNRS UMR 3528, Paris, France

    Massimiliano Bonomi

  2. Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy

    Carlo Camilloni

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Sugita, Y., Kamiya, M., Oshima, H., Re, S. (2019). Replica-Exchange Methods for Biomolecular Simulations. In: Bonomi, M., Camilloni, C. (eds) Biomolecular Simulations. Methods in Molecular Biology, vol 2022. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9608-7_7

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  • DOI: https://doi.org/10.1007/978-1-4939-9608-7_7

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