Simulating the Electronic Circular Dichroism Spectra of Photoreversible Peptide Conformations

Electronic circular dichroism (CD) spectroscopy of peptides is one of the most important experimental characterization tools to get insights regarding their structure. Nevertheless, even though highly useful, the reliable simulations of CD spectra result in a complex task. Here, we propose a combination of quantum mechanics/molecular mechanics (QM/MM) methods with a semiempirical Hamiltonian based on the Frenkel excitons theory to efficiently describe the behavior of a model 27-amino acid α-helical peptide in water. Especially, we show how the choice of the QM region, including different possible hydrogen-bonding patterns, can substantially change the final CD spectrum shape. Moreover, we prove that our approach can correctly explain the changes observed in the peptide conformation (from α-helix to α-hairpin) when covalently linked to a protonated retinal-like molecular switch and exposing the system to UVA light, as previously observed by experiment and extensive molecular dynamics. Hence our protocol may be straightforwardly exploited to characterize light-induced conformation changes in photoactive materials and more generally protein folding processes.