Effects of electrostatic interactions on ligand dissociation kinetics

Aykut Erbaş, Monica Olvera de la Cruz, and John F. Marko
Phys. Rev. E 97, 022405 – Published 16 February 2018
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Abstract

We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

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  • Received 27 October 2017

DOI:https://doi.org/10.1103/PhysRevE.97.022405

©2018 American Physical Society

Physics Subject Headings (PhySH)

Physics of Living SystemsPolymers & Soft MatterInterdisciplinary Physics

Authors & Affiliations

Aykut Erbaş

  • Department of Materials Science and Engineering, Department of Molecular Biosciences, and Department of Physics and Astronomy, Northwestern University, Evanston, Illinois 60208, USA

Monica Olvera de la Cruz

  • Department of Materials Science and Engineering, Department of Chemistry, Department of Chemical and Biological Engineering, and Department of Physics and Astronomy, Northwestern University, Evanston, Illinois 60208, USA

John F. Marko

  • Department of Molecular Biosciences and Department of Physics and Astronomy, Northwestern University, Evanston, Illinois 60208, USA

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Vol. 97, Iss. 2 — February 2018

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