A MODEL FOR ION-TRANSPORT ACROSS MEMBRANES - SOLUTION STRUCTURE OF THE IONOPHORE METAL-COMPLEX SALINOMYCIN-NA DETERMINED BY NMR AND MOLECULAR-DYNAMICS CALCULATIONS

The conformational analysis of the ionophore metal complex salinomycin-Na by NMR spectroscopy and molecular dynamics (MD) calculation was carried out in solution to study a model for ion transport across biological membranes. The first NMR solution structure of an ionophore metal complex using NOE-derived distances is reported. The 51 distance constaints derived from a 600-MHz NOESY spectrum of this molecule in the extreme narrowing limit were in agreement with an overall macrocyclic solution structure. The back-calculation of the NOESY spectrum confirmed the reliability of the NOE data. The structure was first refined by MD simulation in vacuo without a sodium ion present and subsequently in solution in the presence of a sodium ion. The complex shows a hydrophobic surface and a hydrophilic core, with the ion coordinated by a distorted pentagonal pyramid of oxygen atoms. Additional free MD simulations with and without the ion provide further information about the exact hinge regions and a possible mechanism of ionophoric action.