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Replica-Exchange Umbrella Sampling Combined with Gaussian Accelerated Molecular Dynamics for Free-Energy Calculation of Biomolecules
journal contributionposted on 2019-09-27, 15:03 authored by Hiraku 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.
three different casespreviously reported onesvarious biomolecular dynamicsreasonable computational costsgaussian accelerated replicaexchange umbrella samplingenergy landscapes reweightedenergy calculations usingenergy landscapesconformational dynamicssystem energyenergy calculationsenergy calculationcomputational resourcescomputational resourcen exponential averagecumulant expansionconformational equilibriaconformational changeboost potentialadenyl kinase>- glycan