Ionic Solution: What Goes Right and Wrong with Continuum Solvation Modeling.

Solvent-mediated electrostatic interactions were well recognized to be important in the structure and function of molecular systems. Ionic interaction is an important component in electrostatic interactions, especially in highly charged molecules, such as nucleic acids. Here, we focus on the quality of the widely used Poisson-Boltzmann surface area (PBSA) continuum models in modeling ionic interactions by comparing with both explicit solvent simulations and the experiment. In this work, the molality-dependent chemical potentials for sodium chloride (NaCl) electrolyte were first simulated in the SPC/E explicit solvent. Our high-quality simulation agrees well with both the previous study and the experiment. Given the free-energy simulations in SPC/E as the benchmark, we used the same sets of snapshots collected in the SPC/E solvent model for PBSA free-energy calculations in the hope to achieve the maximum consistency between the two solvent models. Our comparative analysis shows that the molality-dependent chemical potentials of NaCl were reproduced well with both linear PB and nonlinear PB methods, although nonlinear PB agrees better with SPC/E and the experiment. Our free-energy simulations also show that the presence of salt increases the hydrophobic effect in a nonlinear fashion, in qualitative agreement with previous theoretical studies of Onsager and Samaras. However, the lack of molality-dependency in the nonelectrostatics continuum models dramatically reduces the overall quality of PBSA methods in modeling salt-dependent energetics. These analyses point to further improvements needed for more robust modeling of solvent-mediated interactions by the continuum solvation frameworks.