Open-shell pair interaction energy decomposition analysis (PIEDA): Formulation and application to the hydrogen abstraction in tripeptides

Abstract

An open-shell extension of the pair interaction energy decomposition analysis (PIEDA) within the framework of the fragment molecular orbital (FMO) method is developed. The open-shell PIEDA method allows the analysis of inter- and intramolecular interactions in terms of electrostatic, exchange-repulsion, charge-transfer, dispersion, and optional polarization energies for molecular systems with a radical or high-spin fragment. Taking into account the low computational cost and scalability of the FMO and PIEDA methods, the new scheme provides a means to characterize the stabilization of radical and open-shell sites in biologically relevant species. The open-shell PIEDA is applied to the characterization of intramolecular interactions in capped trialanine upon hydrogen abstraction (HA) at various sites on the peptide. Hydrogen abstraction reaction is the first step in the oxidative pathway initiated by reactive oxygen or nitrogen species, associated with oxidative stress. It is found that HA results in significant geometrical reorganization of the trialanine peptide. Depending on the HA site, terminal interactions in the radical fold conformers may become weaker or stronger compared to the parent molecule, and often change the character of the non-covalent bonding from amide stacking to hydrogen bonding.