MOLECULAR RECOGNITION OF K+ AND NA+ BY VALINOMYCIN IN METHANOL

Potential of mean force (PMF), free energy perturbation (FEP), and mol ecular dynamics (MD) simulations were used to examine the association processes of K+ and Na+ with valinomycin in methanol. The estimated ab solute free energy of binding of Na+ to valinomycin is similar to 1.1 to -2.5 kcal/mol, which is in reasonable agreement with the available experimental value of -1.2 +/- 0.4 kcal/mol. The calculated K+ free en ergies of association through the preferred HyV (isopropyl) face (the Lac (methyl, isopropyl) face was found to be disfavored) of valinomyci n are -7.4 to -12.5 kcal/mol. This range of values overestimates the e xperimental free energy of binding (-6.4 +/- 0.4 kcal/mol) by similar to 1-6.1 kcal/mol, respectively. Graphical analysis and MD trajectorie s at various points of the PMF profiles show that the association/diss ociation processes of K+ and Na+ are qualitatively similar, and the di fference in binding affinity is based on the solvation free energy of the ions in methanol.