Calculation of binding affinities for linear alcohols to α-cyclodextrin by twin-system enveloping distribution sampling simulations

Abstract

Comparison of three variants of the GROMOS force field for carbohydrates, 53A6GLYC, 56A6CARBO_R and a small modification of the latter, referred to as 56A6CARBO_R+, has been conducted by examining the standard binding free enthalpy of linear alcohols from 1-butanol to 1-dodecanol to α-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 53A6GLYC and 56A6CARBO_R+ parameter sets are a little closer to the experimental data than 56A6CARBO_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.