The Stabilization Effect of Agmatine‐Salicylate Ionic Liquids on PARP‐1 for Parkinson's Disease: A Perspective from DFT and MD Simulations

Abstract

The pathogenesis of Parkinson's disease (PD), a chronic degenerative disorder, is influenced by poly(ADP‐ribose) polymerase‐1 (PARP‐1) since its activation is a prerequisite in dopaminergic neuronal cell death. The biocompatible agmatine‐salicylate ionic liquid (i.e., [Agm][Sal2] IL) has shown promising anticancer and non‐cytotoxic characteristics. The stability of the complexes is inferred to be significantly influenced by the water‐mediated hydrogen bonding (H‐bonding) interactions of cations and anions with aromatic amino acids in the presence and absence of water molecules, as established by density functional theory (DFT) calculations of the [Agm]2+ and [Sal]− ions. To identify the structural stability of PARP‐1 in an IL medium, a series of concentrations (mole fraction 0.20–1.00) of ILs with PARP‐1 using molecular dynamics (MD) simulations are studied for 200 ns. While the oxygen atoms in the ─COO− group of [Sal]− anions established strong H‐bonding interactions with the water molecules, the dicationic [Agm]2+ cations formed H‐bonding interactions with the residues of PARP‐1. It is concluded through various analyses that PARP‐1 maintains its structural stability at 0.60–0.80 mole fractions of ILs in an aqueous medium. Thus, this finding signifies [Agm][Sal2] IL as an efficient PARP‐1 stabilizer; with further in vitro studies this IL can aid in the treatments for PD.