Molecular dynamics study on the conformational flexibility and energetics in aqueous solution of methylated beta-cyclodextrins

All possible methylated beta-cyclodextrins (CDs) with C7-symmetry have been studied by molecular dynamics simulations, in gas phase and in water solution. Energetic and structural information were obtained from the trajectory analysis. CD flexibility increases with degree of methylation, very likely due to the concomitant reduction of the intramolecular hydrogen bonds. Solvation-free energy was computed for each of the studied CDs using the MM/GBSA method. An analysis of radial distribution functions was used to determine distribution of solvent molecules around the O2, O3, and O6. The number of solvent molecules around these oxygens decreases with an increase in the degree of methylation. The DeltaS contribution from solvent thus becomes more positive when the degree of methylation increases and, consequently, the overall DeltaG in water diminishes.