A Seamless Grid-Based Interface for Mean-Field QM/MM Coupled with Efficient Solvation Free Energy Calculations

Abstract

Among various models that incorporate solvation effects into first-principles-based electronic structure theory such as density functional theory (DFT), the average solvent electrostatic potential/molecular dynamics (ASEP/MD) method is particularly advantageous. This method explicitly includes the nature of complicated solvent structures that is absent in implicit solvation methods. Because the ASEP/MD method treats only solvent molecule dynamics, it requires less computational cost than the conventional quantum mechanics/molecular mechanics (QM/MM) approaches. Herein, we present a real-space rectangular grid-based method to implement the mean-field QM/MM idea of ASEP/MD to plane-wave DFT, which is termed "DFT in classical explicit solvents", or DFT-CES. By employing a three-dimensional real-space grid as a communication medium, we can treat the electrostatic interactions between the DFT solute and the ASEP sampled from MD simulations in a seamless and straightforward manner. Moreover, we couple a fast and efficient free energy calculation method based on the two-phase thermodynamic (2PT) model with our DFT-CES method, which enables direct and simultaneous computation of the solvation free energies as well as the geometric and electronic responses of a solute of interest under the solvation effect. With the aid of DFT-CES/2PT, we investigate the solvation free energies and detailed solvation thermodynamics for 17 types of organic molecules, which show good agreement with the experimental data. We further compare our simulation results with previous theoretical models and assumptions made for the development of implicit solvation models. We anticipate that our proposed method, DFT-CES/2PT, will enable vast utilization of the ASEP/MD method for investigating solvation properties of materials by using periodic DFT calculations in the future.

Hydration Thermodynamics of Non-Polar Aromatic Hydrocarbons: Comparison of Implicit and Explicit Solvation Models

“…Recently, our group developed a grid-based mean-field QM/MM method, which incorporates the periodic DFT with plane-wave basis set, coupled with the classical MD. For brevity, the QM/MM method is called DFT in Classical Explicit Solvents , namely DFT-CES [ 37 ]. DFT-CES is designed to utilize a very fine three-dimensional rectangular grid as a communication medium between QM and MM subsystems, thereby transferring precise information of and seamlessly to the MM and QM subsystem, respectively, without involving a charge fitting scheme, such as an electrostatic potential (ESP) fitting procedure [ 38 ].…”

“…The 2PT model has been widely tested and proven successful for the quantitative prediction of the thermodynamics and phase behavior of Lennard-Jones particles at various densities [ 43 ], absolute entropy of water molecules [ 44 ] and organic solvents [ 45 ], and the interfacial thermodynamics of various liquids, e.g., surface tensions [ 46 ]. It is further emphasized that the combination of DFT-CES and 2PT has demonstrated a satisfactory description of the of the 17 polar solutes [ 37 ], which were adopted as the official SAMPL0 challenge test set [ 25 ], and of the solid-liquid interfacial tension of water-graphene/graphite system [ 49 ].…”

Solvation free energies for periodic surfaces: comparison of implicit and explicit solvation models

“…45 Herein, we focus on different approximations for the dominant ∆ s ∆ a G inter term, which describes the intermolecular solvent-solute contribution to the free energy of solvation, including the solvent re-organization energy.…”

Determination of the Free Energies of Mixing of Organic Solutions through a Combined Molecular Dynamics and Bayesian Statistics Approach

“…We note that two different non-bonded parameters for iodine were evaluated and the input files are included in the SI, with the one that presented the best agreement with the experimental DIO density being used in all subsequent calculations. Although the 2PT method has been widely applied to liquids and even mixtures, most of the simulation targets have been ions, non-organic liquids, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] or water/organic mixtures. 13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] The validation of using 2PT on pure organic solvents here provides confidence in the application of the method for binary organic mixtures.…”

“…Since the inception of the 2PT method, it has been shown to provide accurate determinations of the absolute entropies and free energies for a variety of chemical systems, including those with considerable chemical and physical complexity. 13,14,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Returning to the concept of printing, when considering solution drying, e.g. as the solvent in an ink formulation dries to leave behind a thin film, the relative concentrations of the primary solvent and all solution components are continuously changing.…”