Biophysical Reviews

, Volume 11, Issue 3, pp 457–469 | Cite as

Molecular simulations by generalized-ensemble algorithms in isothermal–isobaric ensemble

  • Masataka Yamauchi
  • Yoshiharu Mori
  • Hisashi OkumuraEmail author


Generalized-ensemble algorithms are powerful techniques for investigating biomolecules such as protein, DNA, lipid membrane, and glycan. The generalized-ensemble algorithms were originally developed in the canonical ensemble. On the other hand, not only temperature but also pressure is controlled in experiments. Additionally, pressure is used as perturbation to study relationship between function and structure of biomolecules. For this reason, it is important to perform efficient conformation sampling based on the isothermal–isobaric ensemble. In this article, we review a series of the generalized-ensemble algorithms in the isothermal–isobaric ensemble: multibaric–multithermal, pressure- and temperature-simulated tempering, replica-exchange, and replica-permutation methods. These methods achieve more efficient simulation than the conventional isothermal–isobaric simulation. Furthermore, the isothermal–isobaric generalized-ensemble simulation samples conformations of biomolecules from wider range of temperature and pressure. Thus, we can estimate physical quantities more accurately at any temperature and pressure values. The applications to the biomolecular system are also presented.


Generalized-ensemble algorithm Molecular simulation High pressure Protein folding 



This work was supported by JSPS KAKENHI (no. JP16H00790) and the Okazaki Orion Project of National Institutes of Natural Sciences.

Compliance with Ethical Standards

Conflict of interest

Masataka Yamauchi declares that he has no conflict of interest. Yoshiharu Mori declares that he has no conflict of interest. Hisashi Okumura declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Structural Molecular ScienceSOKENDAI (The Graduate University for Advanced Studies)OkazakiJapan
  2. 2.Exploratory Research Center on Life and Living Systems (ExCELLS)National Institutes of Natural SciencesOkazakiJapan
  3. 3.Institute for Molecular Science (IMS)National Institutes of Natural SciencesOkazakiJapan
  4. 4.School of PharmacyKitasato UniversityShirokane, Minato-kuJapan

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