P. Cieplak et al., WALKING ON THE FREE-ENERGY HYPERSURFACE OF THE 18-CROWN-6 ION SYSTEM USING FREE-ENERGY DERIVATIVES, The Journal of chemical physics, 101(1), 1994, pp. 627-633
Molecular dynamics simulations have been used to calculate free energy
derivatives with respect to nonbonded parameters for both ions and th
e host, 18-crown-6 in cation-18-crown-6 complexes. The free energy der
ivatives have been used to examine the free energy hypersurface for su
ch complexes and to ''predict'' the optimal cationic ligand for 18-cro
wn-6 complexation in aqueous solution. This method has promise to enab
le the refinement of the intermolecular interaction parameters for bot
h hosts and guests in aqueous solution. In particular, we show that th
e optimal ion size for 18-crown-6 is calculated to be between the size
s of Na+ and K+, consistent with the experimental data. More generally
, it has potential to be a powerful tool in computer aided molecular d
esign.