Conformational free energies of methyl-alpha-L-iduronic and methyl-beta-D-glucuronic acids in water.
We present a simulation protocol that allows for efficient sampling of the degrees of freedom of a solute in explicit solvent. The protocol involves using a nonequilibrium umbrella sampling method, in this case, the recently developed adaptively biased molecular dynamics method, to compute an approximate free energy for the slow modes of the solute in explicit solvent. This approximate free energy is then used to set up a Hamiltonian replica exchange scheme that samples both from biased and unbiased distributions. The final accurate free energy is recovered via the weighted histogram analysis technique applied to all the replicas, and equilibrium properties of the solute are computed from the unbiased trajectory. We illustrate the approach by applying it to the study of the puckering landscapes of the methyl glycosides of alpha-L-iduronic acid and its C5 epimer beta-D-glucuronic acid in water. Big savings in computational resources are gained in comparison to the standard parallel tempering method.
Babin
Volodymyr
V
Department of Physics and Center for High Performance Simulations (CHiPS), North Carolina State University, Raleigh, North Carolina 27695, USA. vbabin@ncsu.edu
Sagui
Celeste
C
D000465:Algorithms; D002240:Carbohydrate Sequence; D003198:Computer Simulation; D020723:Glucuronic Acid / Q000737:chemistry*; D007067:Iduronic Acid / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D014867:Water; D007067:Iduronic Acid; D020723:Glucuronic Acid