Theoretical ECD calculations – a useful tool for estimating the conformational change of a ligand in the binding pocket of proteins

Abstract

The correlation of experimentally induced circular dichroism (ICD) spectra recorded from (a)chiral ligands during their binding to proteins with simulated electronic circular dichroism (ECD) spectra via time-dependent density functional theory calculations was used for obtaining structural information on the ligands in the protein binding sites. A three step procedure is reported, involving the optimization of the most relevant conformers of the different ligand species presumed to be present in the system, the calculation of their ECD spectra and the comparison of the theoretical spectra with the experimental ones. This approach was exemplified for several model systems that can yield ICD signals through steric hindrance of a degree of freedom in the protein pocket. The method was found to be suitable to identify the bound form(s) for flexible molecular systems in which several species can coexist in solution. The effect of several functional/basis set combinations was tested, aiming to establish which one gives the most reliable results.