posted on 2019-09-27, 15:03authored byHiraku Oshima, Suyong Re, Yuji Sugita
We
have developed an enhanced conformational sampling method combining
replica-exchange umbrella sampling (REUS) with Gaussian accelerated
molecular dynamics (GaMD). REUS enhances the sampling along predefined
reaction coordinates, while GaMD accelerates the conformational dynamics
by adding a boost potential to the system energy. The method, which
we call GaREUS (Gaussian accelerated replica-exchange umbrella sampling),
enhances the sampling more efficiently than REUS or GaMD, while the
computational resource for GaREUS is the same as that required for
REUS. The two-step reweighting procedure using the multistate Bennett
acceptance ratio method and the cumulant expansion for the exponential
average is applied to the simulation trajectories for obtaining the
unbiased free-energy landscapes. We apply GaREUS to the calculations
of free-energy landscapes for three different cases: conformational
equilibria of N-glycan, folding of chignolin, and
conformational change of adenyl kinase. We show that GaREUS speeds
up the convergences of free-energy calculations using the same amount
of computational resources as REUS. The free-energy landscapes reweighted
from the trajectories of GaREUS agree with previously reported ones.
GaREUS is applicable to free-energy calculations of various biomolecular
dynamics and functions with reasonable computational costs.