Charge density effect in counter ion condensation on RNA.

Abstract

Screening the negatively charged nucleic acid backbone by counter ions is essential for its folding and function. Experimental and computational studies demonstrate the influence of charge density on stability and cation distributions for RNA/DNA duplexes [1-3]. However, a detailed understanding of its thermodynamics aspects remains elusive. We address this question by studying the effect of charge density on the energy landscape of the counterion condensation process in the context of G-Quadruplex RNA. Metadynamics simulations that allow navigating the free energy surface (FES) of the fraction of screened charge variable provided a thermodynamics picture of the condensation process. We study the monovalent ion salt series with decreasing charge density, Li+, Na+, K+, Cs+, and Rb+. We found that the counterion condensation process has a single minimum irrespective of the charge density. Surprisingly, the minima are located at around 70-75% charge screening for all monovalent ions under study, consistent with mean field theories. However, unlike mean-field theories, the screening is influenced by charge density. The degree of screening varied in the order of Li+>Na+≈Cs+≈Rb+>K+. The most notable observation is that K+ shows a non-monotonic trend with its charge density. We investigate the structural and energetic factors that give rise to the differences in charge screening. Our analysis demonstrates that hydration and preferential binding dictate the charge density-induced screening effect. Together, our study offers detailed insight into the charge compensating cations and highlights the unique properties of K+, leading to its lower screening.