Role of Native and Zwitterionic Glycine in Electron Attachment to DNA: From Dipole-Bound to Solvent-Bound Doorway States

Abstract

Electron attachment to DNA is strongly influenced by its molecular environment, yet the role of amino acids under physiologically relevant conditions remains poorly understood. Here, we investigate the effect of native and zwitterionic glycine on electron attachment to thymine using high-level electron-affinity calculations and QM/MM molecular dynamics simulations. Under micro-solvated conditions, electron attachment occurs through a dipole-bound doorway state that evolves into a valence-bound anion via nonadiabatic coupling. The zwitterionic form of glycine strengthens stabilization of the diffuse electron owing to its larger internal charge separation, whereas the stability of the valence-bound anion is determined by the hydrogen-bonding geometry. Barrier-free proton transfer is observed only for specific binding motifs and substantially stabilizes the thymine-centered anion. In bulk solution, the doorway mechanism persists, with a solvent-bound state replacing the dipole-bound state as the initial electron-trapping state. The larger electrostatic field of zwitterionic glycine delays electron localization on thymine, while permanent proton transfer is observed only in selected native glycine trajectories and is absent throughout the present simulations of zwitterionic glycine. Despite these differences in electron-transfer dynamics, both amino acid forms provide similar stabilization of the thymine-centered anion after solvent reorganization. Our results establish the solvent-bound state as the condensed-phase analogue of the dipole-bound doorway state and reveal how amino acid environments modulate electron attachment pathways in realistic DNA systems.