Free energy simulations of D-xylose in water and methyl D-xylopyranoside in methanol

Free energy simulations have been performed to analyze the anomeric equilibrium of D-xylose in water and methyl D-xyloside in methanol. The anomeric alpha/beta ratios were determined experimentally by H-1 NMR spectroscopy. The molecular dynamics simulations employed the canonical ensemble to calculate the Helmholtz free energy change (DeltaA). The free energy perturbation and the thermodynamic integration methods were used for the evaluation. The duration of simulations was 500 ps with 18 and 24 lambda -points in water and methanol, respectively. The relative free energy change Delta DeltaA(solv-gas) calculated as beta-alpha was for both solvents small, less than or equal to0.3 kcal, but favored different anomeric configurations. Analysis of solvent structure indicated that the beta -anomeric form possessed greater hydrogen bond ability at the anomeric center in xylose, whereas for the methyl xyloside there was no significant difference.