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

Abstract

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 PBSA continuum models in modeling ionic interactions by comparing with both explicit solvent simulations and 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 previous study and 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, though nonlinear PB agrees better with SPC/E and 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 non-electrostatics continuum models dramatically reduces the overall quality of PBSA methods in modeling salt-dependent energetics. These analyses points to further improvements needed for more robust modeling of solvent-mediate interactions by the continuum solvation frameworks.

Molecular Mechanism of Loading Sulfur Hexafluoride in γ-Cyclodextrin Metal–Organic Framework

“…Molecular modeling has been widely used in the interpretation of experimental results in diverse fields. , Molecular modeling can quantitatively predict the uptake of simple gas, yet it is not easy to predict the selectivity in the case of mixtures and provide a detailed picture on the molecular scale . Molecular docking is a method, which predicts the preferred orientation of one molecule to a second when molecules interact with each other to form a stable complex .…”

Estimating the Roles of Protonation and Electronic Polarization in Absolute Binding Affinity Simulations

“…88−110 PBSA coupled with the MBAR protocol (i.e., MBAR/PBSA) was developed as an alternative to computing the decharging free energy for alchemical simulations in explicit solvent. 111 The original explicit solvent trajectories for all lambda windows used for decharging were prepared by stripping the waters and ions, except for the counterion used to maintain the ligand charge neutrality.…”

“…MBAR/PBSA) was developed as an alternative to computing the decharging free energy for alchemical simulations in explicit solvent. 111 The original explicit solvent trajectories for all lambda windows used for decharging were prepared by stripping the waters and ions, but with the counter-ion used to maintain the ligand charge neutrality kept. MBAR/PBSA energy evaluation was performed via the linear Poisson-Boltzmann (LPB) method with the Amber18 sander module 112 by post-processing solvent-stripped snapshots from alchemical simulations.…”

Dielectric continuum methods for quantum chemistry

“…7,68,[77][78][79] Within the biomolecular electrostatics community there has been significant discussion regarding the accuracy of the linearization approximation, with various studies noting that the nonlinear form affords better agreement with explicit solvent simulations when the ionic strength is high. 75,80 Deficiencies in the Poisson-Boltzmann model itself (even in its nonlinear form and especially for polyvalent ions) have also been pointed out. 81 These arise due to statistical correlations between ion positions that are neglected by the model in Equation (2.13).…”