Molecular Simulations of Ion Effects on the Thermodynamics of RNA Folding

Denesyuk, Natalia A.; Hori, Naoto; Thirumalai, D.

Abstract

How ions affect RNA folding thermodynamics and kinetics is an important but a vexing problem that remains unsolved. Experiments have shown that the free-energy change, δG(c), of RNA upon folding varies with the salt concentration (c) as, δG(c) = k c ln c + const, where the coefficient k c is proportional to the difference in the ion preferential coefficient, δ?. We performed simulations of a coarse-grained model, by modeling electrostatic interactions implicitly and with explicit representation of ions, to elucidate the molecular underpinnings of the relationship between δG and δ?. The simulations quantitatively reproduce the heat capacity for a pseudoknot, thus validating the model. We show that δG(c), calculated directly from δ?, varies linearly with ln c (c < 0.2 M), for a hairpin and the pseudoknot, demonstrating a molecular link between the two quantities. Explicit ion simulations also show the linear dependence of δG(c) on ln c at all c with k c = 2k B T, except that δG(c) values are shifted by ∼2 kcal/mol higher than experiments. The discrepancy is due to an underestimation of for both the folded and unfolded states while giving accurate values for δ?. The predictions for the salt dependence of δare amenable to test using single-molecule pulling experiments. The framework provided here can be used to obtain accurate thermodynamics for other RNA molecules as well.

Citation

Denesyuk, N. A., Hori, N., & Thirumalai, D. (2018). Molecular Simulations of Ion Effects on the Thermodynamics of RNA Folding. Journal of Physical Chemistry B, 122(50), 11860-11867. https://doi.org/10.1021/acs.jpcb.8b08142

• Journal Article Type: Article
• Acceptance Date: Nov 23, 2018
• Online Publication Date: Nov 23, 2018
• Publication Date: Dec 20, 2018
• Deposit Date: Sep 19, 2020
• Publicly Available Date: Feb 16, 2021
• Journal: The Journal of Physical Chemistry B
• Print ISSN: 1520-6106
• Electronic ISSN: 1520-5207
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 122
• Issue: 50
• Pages: 11860-11867
• DOI: https://doi.org/10.1021/acs.jpcb.8b08142
• Keywords: Physical and Theoretical Chemistry; Materials Chemistry; Surfaces, Coatings and Films
• Public URL: https://nottingham-repository.worktribe.com/output/4342465
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.jpcb.8b08142
• Additional Information: This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in The Journal of Physical Chemistry B, copyright © American Chemical Society after peer review. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jpcb.8b08142#