Comparison of estimates of free energy for binding of mono- and di-substituted benzenes with α-cyclodextrin obtained by single-step perturbation and thermodynamic integration

Abstract

In this work, the relative free energies of binding individual members of a series of mono- and di-substituted benzenes to α-cyclodextrin in water have been estimated using the single step perturbation methodology (SSP). The computations involved were based on 5 ns molecular dynamics simulations of a judiciously chosen unphysical reference state and its complex with α-CD in water. The thermodynamic integration method (TI) was also used to calculate the relative free energies of binding for comparison purposes. The results of SSP computations were in good agreement with experimental data. The results also show that the SSP technique exhibits a potential alternative to more traditional but more expensive free energy computational methods.