MOLECULAR-DYNAMICS SIMULATIONS OF VALINOMYCIN AND ITS POTASSIUM COMPLEX IN HOMOGENEOUS SOLVENTS

Molecular dynamics simulations of kalinomycin (VM) and its potassium c omplex in water and in a Lennard Jones solvent are reported, In agreem ent with experimental evidence the structure of K+-VM in nonpolar solu tion 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 dimet hyl sulfoxide (DMSO). However, also in agreement with spectroscopic da ta 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 dec omplexation of K+-VM in water, with the ion passing through the HyV fa ce in preference to the Lac face. Water attack was observed through bo th faces. The time scale for all conformational transitions is of the order of 100 ps, with structural changes associated with the (de)-comp lexation reaction controlled by the ring dihedrals in the vicinity of the L-lactic acid residues. Global structural functions, radial distri bution functions, and VM ring dihedral analysis are presented, along w ith an analysis of the decomplexation event.