Dependence of the average energy between the 1:2 complexes of enantiomeric α-pinenes with α-cyclodextrin on the length of dynamic simulation

Abstract

Molecular dynamics is frequently used in studies of chiral recognition by cyclodextrins. Although the free energy difference for complexes involving enantiomeric guests is a measure of this effect, the difference between the corresponding average energies is used instead in the pertaining literature with simulation times mostly not exceeding 2 ns. In continuation of our program of evaluation of theoretical methods applied in cyclodextrin studies, we have carried out simulations for 12 ns for the 1:2 complexes of α-pinenes with α-cyclodextrin in water and analyzed how the average energy differences depended on the length of simulation time. Surprisingly, not only the value of energy difference but also its sign changed during the simulations. This result indicates that much longer simulation times are necessary to obtain reliable results from dynamic simulations.