Europium Coordination Structure in Peptide Complexes Resolved with Simulation and X-ray Absorption Spectroscopy

The study of the coordination structure in lanthanide-ligand complexes is important to gain insight into the selectivity of ligands for specific lanthanide ions. We recently designed lanthanide binding cyclic peptides (LBCPs), which display selectivity toward the middle lanthanides. In this study, we report micromolar affinity in a Eu-LBCP complex and resolve the structure of the europium complexes with two LBCPs by comparing experimental extended X-ray absorption fine structure (EXAFS) spectra to ensemble-average spectra derived from molecular dynamics (MD) simulation, as well as to spectra from a fitting model. Our results show agreement between the computationally derived and experimentally measured EXAFS spectra, which supports the predicted Eu coordination structure in LBCP complexes, as well as the utility of combining molecular simulation and EXAFS to study the structure of lanthanide-ligand complexes in solution.