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Drug Design by Generalized-Ensemble Simulations

[ Vol. 17 , Issue. 17 ]

Author(s):

Yuko Okamoto   Pages 1758 - 1772 ( 15 )

Abstract:


In pharmaceutical design based on molecular simulations, one faces a great difficulty. Conventional simulations in the canonical ensemble are of little use, because they tend to get trapped in some of the local-minimum-energy states that exist in a huge number. A simulation in generalized ensemble performs a random walk in potential energy space and can overcome this difficulty.

In this article we review a few of powerful generalized-ensemble algorithms, namely, replica-exchange method, multidimensional replica- exchange method, and replica-exchange umbrella sampling. The effectiveness of the methods is tested with ligand and short peptide systems.

Keywords:

Molecular simulation,drug design,generalized-ensemble algorithm,replica-exchange molecular dynamics (REMD),replicaexchange umbrella sampling (REUS),REMD,REUS,canonical,Hamiltonian,isobaric,isothermal,Metropolis,probability,replica,histogram,trajectory,multivariable,dynamics,dielectric,Met-enkephalin

Affiliation:

Department of Physics, School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan.



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