Electrostatic effects on facilitated dissociation of molecular ligands

Electrostatic interactions between molecular ligands and their binding sites control many aspects in biomachinery from gene regulation to molecular recognition. In this study, unbinding of multivalent cationic ligands from charged polymeric binding sites is considered. Our molecular dynamics (MD) study is inspried by the good accord between the experiments and MD simulations of single-molecule studies of protein-DNA interactions (Kamar et al, PNAS, 2017). We consider univalent salt concentrations spanning a thousandfold range, together with various concentrations of excess ligands to reveal the ionic effects on spontaneous and facilitated dissociation (FD) unbinding mechanisms. We treat electrostatic interactions both at a Debye-H\”{u}ckel level, as well as by the more precise approach of considering all ionic species explicitly. Both treatments show that salt dependence of FD process becomes weaker with increasing free ligand concentration. Our simulations also predict a variety of FD regimes as a function of free ligand concentration (Erbas et al, arXiv, 2017).