Refinement of Multisite Ion Model through Simulation of Osmotic Pressure: Applications on Ion-Mediated Calculations of SsRNA

Abstract

Accurate force field parameters for ions are essential for meaningful simulation studies of proteins and nucleic acids. Currently accepted models of ions, especially for divalent ions, do not necessarily reproduce the right physiological behavior. In our previous work, we found a model, called the multisite-ion model, where instead of treating the ions as an isolated sphere, we split the charge into multiple sites (Saxena et al, 2013). With this new model, we were not only able to achieve accurate coordination geometries around the ion, but were also able to predict better free energies for proteins and nucleic acids. Here, we further refine the model by focusing on the behavior of divalent ions in concentrated electrolyte solutions. With several ions present in water, it is important that there are no artifacts such as unusual ion-ion pairing or crystallization. Recently, Luo and Roux showed that osmotic pressure could be successfully used for refinement of ion parameters in NaCl and KCl solutions. We use the same method to test and calibrate the multisite-model of Mg2+ and Ca2+ in concentrated solution with Cl-. We find that after refinement the solution gets rid of direct ion-pairs, matching the experimentally observed behavior. Subsequently, we use the refined parameters to observe the dependence of counterions on the flexibility of ssRNA. We compare our results to smFRET experiments by Chen et al, which show that Mg2+ has more charge screening efficiency than Na+ on a 40-mer uridylate (rU40).Saxena, A., & Sept, D. (2013). JCTC, 9(8), 3538-3542.Luo, Y., & Roux, B. (2010). J. Phys. Chem. Lett, 1(1), 183-189.Chen, H., Meisburger, S. P., Pabit, S. A., Sutton, J. L., Webb, W. W., & Pollack, L. (2012). PNAS, 109(3), 799-804.