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Fluid Phase Equilibria, Vol.422, 1-17, 2016
Calculation of binding affinities for linear alcohols to alpha-cyclodextrin by twin-system enveloping distribution sampling simulations
Comparison of three variants of the GROMOS force field for carbohydrates, 53A6(GLYC), 56A6(CARBO_R) and a small modification of the latter, referred to as 56A6(CARBO_R+), has been conducted by examining the standard binding free enthalpy of linear alcohols from 1-butanol to 1-dodecanol to alpha-cyclodextrin in aqueous solution. The double decoupling approach was employed to calculate the standard binding free enthalpy of 1-hexanol, while for all other compounds relative binding free enthalpies for pairs of alcohols differing by two carbon atoms were calculated from twin-system enveloping distribution sampling simulations. While all three force fields slightly overestimate the magnitude of the standard binding free enthalpy of 1-hexanol the 53A6(GLYC) and 56A6(CARBO_R+) parameter sets are a little closer to the experimental data than 56A6(CARBO_R). For relative binding free enthalpies no significant difference between the force fields was observed. All three force fields support those experimental measurements that found a distinct increase in the binding affinity with increasing number of carbon atoms even for longer chain lengths up to 1-dodecanol. (C) 2016 Elsevier B.V. All rights reserved.