Computational study of copper binding to DAHK peptide

Abstract

Ligand Field Molecular Mechanics (LFMM), Density Functional Theory (DFT) and Semi-Empirical methods are used to study Cu(II) binding to the tetrapeptide Asp-Ala-His-Lys (DAHK). Two conformational searching tools, LFMM/AMBER and CREST/xTB, are used to predict the energy and geometry of Cu-DAHK, using DFT as a benchmark. In addition, DFT-predicted electronic spectra are used to evaluate the binding modes found. LFMM and DFT reproduce the experimentally determined coordination, a distorted square planar arrangement of 4 nitrogen ligands with axial coordination to a fifth, oxygen ligand. However, CREST conformational search was unsuccessful in predicting the coordination mode of Cu-DAHK, changing the bonding equatorial ligands from 4 N to 3N1O.