Characterization of β-turns by electronic circular dichroism spectroscopy: a coupled molecular dynamics and time-dependent density functional theory computational study

Electronic circular dichroism is one of the most used spectroscopic techniques for peptide and protein structural characterization. However, while valuable experimental spectra exist for alpha-helix, beta-sheet and random coil secondary structures, previous studies showed important discrepancies for beta-turns, limiting their use as a reference for structural studies. In this paper, we simulated circular dichroism spectra for the best-characterized beta-turns in peptides, namely types I, II, I ' and II '. In particular, by combining classical molecular dynamics simulations and state-of-the-art quantum time-dependent density functional theory (with the polarizable embedding multiscale model) computations, two common electronic circular dichroism patterns were found for couples of beta-turn types (namely, type I/type II ' and type II/type I '), at first for a minimal di-peptide model (Ace-Ala-Ala-NHMe), but also for all sequences tested with non-aromatic residues in the central positions. On the other hand, as expected, aromatic substitution causes important perturbations to the previously found ECD patterns. Finally, by applying suitable approximations, these patterns were subsequently rationalized based on the exciton chirality rule. All these results provide useful predictions and pave the way for a possible experimental characterization of beta-turns based on circular dichroism spectroscopy.