This book presents the generalized-ensemble algorithms, which are powerful algorithms to simulate complex systems and greatly speed up the convergence to thermal equilibrium. By using the algorithms, one can perform random walks of certain physical quantities or their conjugate parameters, which alleviates the difficulty of conventional methods in which simulations tend to get trapped in states of local-minimum free energy states.

In this book, one of the most commonly used generalized-ensemble algorithms, namely, replica-exchange method (REM) is explained first. The original version performs a random walk in temperature space. The authors then present various extensions of REM by introducing multidimensional replica-exchange method in which multivariable random walks are realized by further enhancing the configurational sampling. Other generalized-ensemble algorithms are also presented for wide applications to many complex systems.

The book explains the basic ideas in detail, and it is not only useful for researchers in academia and industry in the field of computational physics, chemistry, biology, pharmacology, medicine, materials science but also can be used as a textbook for undergraduate and graduate students. 

Yuji Sugita received his B.S.(1993), M.S.(1995), and Ph.D. (1998) in chemistry from Kyoto University. After his postdoctoral work at RIKEN, he worked as a research associate at the Institute for Molecular Science from 1998 to 2002. He moved to the Institute for Molecular and Cellular Biology, the University of Tokyo as a lecturer in 2002. He then became an associate chief scientist in RIKEN in 2007 and has been promoted to be a chief scientist in RIKEN since 2012. He has also worked as a team leader of the RIKEN Center for Computational Science (currently as a team principal) and the RIKEN Center for Biosystems Dynamics Research (until March 2025). Since October 2025, he has also worked as a professor at the Department of Physics, the University of Tokyo. His research has focused on the development of enhanced sampling methods and multi-scale molecular dynamics software, and their application to biomolecular structure, dynamics, and function relationships in cellular environments.

Yuko Okamoto received his B.S. and M.S. in physics from Brown University in 1979 and Ph.D. in physics from Cornell University in 1984. After his postdoctoral work at Virginia Polytechnic Institute and State University in 1984–1986, he worked as an assistant professor (later, an associate professor) at Nara Women’s University from 1986 to 1995. He moved to the Institute for Molecular Science and the Graduate University for Advanced Studies in 1995 as an associate professor. He then became a professor of biophysics at Nagoya University in 2005. He has been a professor emeritus of Nagoya University since he retired from it in 2022. His research has focused on the development of enhanced sampling methods in molecular simulations, for example, replica-exchange molecular dynamics and other generalized-ensemble algorithms, and their applications to computational physics/chemistry/biology problems such as protein folding, ligand binding, and prediction of three-dimensional structures of molecules.