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

Abstract

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.

Visualizing Cyclic Peptide Hydration at the Single-Molecule Level

“…By analyzing the chemical structure (Figure 1a), we determined that valinomycin contains two types of carbonyls: ester carbonyls and amide carbonyls. As shown in Tables 1 and 2, the carbonyl oxygen is the energetically favorable binding site and has the most potential to participate in the formation of hydrogen bonds with water molecules151618. In addition, water molecules have the ability to bind with ester oxygens and amide nitrogens.…”

“…Until now, the role of water in a selective transport mechanism has not been clear. The determination of the structure that valinomycin adopts at the water/membrane interface and valinomycin-water interactions using modern experimental techniques remains huge challenge because valinomycin is practically insoluble in water and the K + -valinomycin complexes are unstable in water1819. Herein, we remove these experimental obstacles by introducing gaseous water and valinomycin onto a Cu(111) surface under ultra-high vacuum (UHV) conditions.…”

Rethinking Ion Transport by Ionophores: Experimental and Computational Investigation of Single Water Hydration in Valinomycin-K+ Complexes

“…When bound to K + , it forms a C 3 -symmetrical, “bracelet” structure (Figure b and c) with the main chain folded in a β-turn-like manner (see Figure c). It is highly selective in binding K + over Na + , based on both thermodynamic and structural arguments. , Conformational changes of valinomycin during the catch and release of K + have been extensively studied with nuclear magnetic resonance (NMR), vibrational circular dichroism, Raman spectroscopy, solution-phase infrared (IR) spectroscopy, X-ray crystallography, and molecular dynamics simulations. − The central polar cavity has the K + octahedrally coordinated to six ester carbonyls. The hydrophobic side chains point outwardly, shielding the ion while inside the hydrophobic cellular membrane.…”

“…The changes in structure, based on the calculations, can be seen using two metrics for the ion-cluster geometries, i.e., , the asphericity order parameter, , A 3 , with limiting values of 0 for a perfect sphere and 1.0 for an infinitely thin rod, and the mean-squared radius of gyration, , S 2 , which provides a mass-weighted size ( S 2 = 3 r 2 /5 for a uniform solid sphere). where λ i are the moments of inertia, m i and r i are the mass and position of each atom, respectively, r COM is the center of mass, n is the number of atoms, and M is the mass of the cluster.…”

“…As can be seen, the assignments of the conformers to specific spectral features and the relative contributions to the overall ensemble are supported by consistent ordering of the vibrational frequencies, separation of the two OH bands for each conformer, and comparison with similar systems and the relative intensities of observed bands. The changes in structure, based on the calculations, can be seen using two metrics for the ion-cluster geometries, i.e., 6,7 the asphericity order parameter, 39,40 A 3 , with limiting values of 0 for a perfect sphere and 1.0 for an infinitely thin rod, and the mean-squared radius of gyration, 6,7 S 2 , which provides a massweighted size (S 2 = 3r 2 /5 for a uniform solid sphere).…”