A new simulated tempering method, which is referred to as simulated tempering umbrella sampling, for calculating the free energy of chemical reactions is proposed. First principles molecular dynamics simulations with this simulated tempering were per
formed in order to study the intramolecular proton transfer reaction of malonaldehyde in aqueous solution. Conformational sampling in reaction coordinate space can be easily enhanced with this method, and the free energy along a reaction coordinate can be calculated accurately. Moreover, the simulated tempering umbrella sampling provides trajectory data more efficiently than the conventional umbrella sampling method.
In biomolecular systems (especially all-atom models) with many degrees of freedom such as proteins and nucleic acids, there exist an astronomically large number of local-minimum-energy states. Conventional simulations in the canonical ensemble are of
little use, because they tend to get trapped in states of these energy local minima. Enhanced conformational sampling techniques are thus in great demand. A simulation in generalized ensemble performs a random walk in potential energy space and can overcome this difficulty. From only one simulation run, one can obtain canonical-ensemble averages of physical quantities as functions of temperature by the single-histogram and/or multiple-histogram reweighting techniques. In this article we review uses of the generalized-ensemble algorithms in biomolecular systems. Three well-known methods, namely, multicanonical algorithm, simulated tempering, and replica-exchange method, are described first. Both Monte Carlo and molecular dynami
We present generalized-ensemble algorithms for isobaric-isothermal molecular simulations. In addition to the multibaric-multithermal algorithm and replica-exchange method for the isobaric-isothermal ensemble, which have already been proposed, we prop
ose a simulated tempering method for this ensemble. We performed molecular dynamics simulations with these algorithms for an alanine dipeptide system in explicit water molecules to test the effectiveness of the algorithms. We found that these generalized-ensemble algorithms are all useful for conformational sampling of biomolecular systems in the isobaric-isothermal ensemble.
In the replica-exchange molecular dynamics method, where constant-temperature molecular dynamics simulations are performed in each replica, one usually rescales the momentum of each particle after replica exchange. This rescaling method had previousl
y been worked out only for the Gaussian constraint method. In this letter, we present momentum rescaling formulae for four other commonly used constant-temperature algorithms, namely, Langevin dynamics, Andersen algorithm, Nos{e}-Hoover thermostat, and Nos{e}-Poincar{e} thermostat. The effectiveness of these rescaling methods is tested with a small biomolecular system, and it is shown that proper momentum rescaling is necessary to obtain correct results in the canonical ensemble.
