Molecular dynamics simulations of valinomycin and its potassium complex in homogeneous solvents

Molecular dynamics simulations of kalinomycin (VM) and its potassium complex in water and in a Lennard Jones solvent are reported. In agreement with experimental evidence the structure of K(+)-VM in nonpolar solution is similar to the solid state structure whereas the structure of uncomplexed VM is not. In water uncomplexed VM retains the Lac and HyV faces (which are lost in nonpolar solution) and shows some similarity with the solid-state structure obtained by crystallization from dimethyl sulfoxide (DMSO). However, also in agreement with spectroscopic data a dynamic equilibrium between a set of conformers is established in both solvents. Our model reproduces the experimental dipole moment (3.6 D) of VM in nonpolar solution. We also observed the spontaneous decomplexation of K(+)-VM in water, with the ion passing through the HyV face in preference to the Lac face. Water attack was observed through both faces. The time scale for all conformational transitions is of the order of 100 ps, with structural changes associated with the (de)-complexation reaction controlled by the ring dihedrals in the vicinity of the L-lactic acid residues. Global structural functions, radial distribution functions, and VM ring dihedral analysis are presented, along with an analysis of the decomplexation event.