Computational Study of Arsenite Binding to Tetraglycine: Structural and Energetic Insights

Peptides are versatile biomolecules that have emerged as promising scaffolds for chemical recognition. Probing their interactions with toxic oxyanions such as arsenite is important for understanding fundamental recognition mechanisms relevant to environmental chemistry. In this study, the affinity of a tetraglycine peptide, (Gly) ${}_4$ , toward the dihydrogen arsenite, $H_2{\mathrm{AsO}}_3^{-}$ , is investigated using a multilevel computational approach. MD simulations identify the stable conformational landscape of tetraglycine, revealing the emergence of a preorganized pseudo-macrocyclic motif. Density functional theory (DFT) provides detailed insights into the electronic features of the peptide-anion interaction, highlighting cooperative hydrogen bonding at the binding interface. An ONIOM-based QM/MM framework incorporates explicit solvation on the (Gly) ${}_4$ -anion complex, emphasizing the role of backbone flexibility in stabilizing the bound structure. Noncovalent interaction (NCI) and symmetry-adapted perturbation theory (SAPT0) analysis indicate that electrostatic interactions constitute the dominant stabilizing contribution. These findings deepen the mechanistic understanding of peptide-anion interactions while clarifying the scope and limitations of this simplified model system.