Dispersion and repulsion contributions to the solvation energy: Refinements to a simple computational model in the continuum approximation (original) (raw)
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The Journal of Physical Chemistry, 1996
Electrostatic solvation free energies are calculated using a self consistent reaction field (SCRF) procedure that combines a continuum dielectric model of the solvent with both Hartree-Fock (HF) and density functional theory (DFT) for the solute. Several molecules are studied in aqueous solution. They comprise three groups: nonpolar neutral, polar neutral, and ionic. The calculated values of ∆G el are sensitive to the atomic radii used to define the solute molecular surface, particularly to the value of the hydrogen radius. However, the values of ∆G el exhibit reasonable correlation with experiment when a previously determined, physically motivated set of atomic radii were used to define the van der Waals surface of the solute. The standard deviation between theory and experiment is 2.51 kcal/mol for HF and 2.21 kcal/mol for DFT for the 14 molecules examined. The errors with HF or DFT are similar. The relative difference between the calculated values of ∆G el and experiment is largest for nonpolar neutral molecules, intermediate for polar neutral molecules, and smallest for ions. This is consistent with the expected relative importance of nonelectrostatic contributions to the free energy that are omitted in the model.
Electrostatic component of solvation: Comparison of SCRF continuum models
Journal of Computational Chemistry, 2003
We report a systematic comparison of the electrostatic contributions to the free energy of solvation from three different kinds of quantum mechanical self-consistent reaction field (SCRF) methods. We also compare the liquid-phase dipole moments as a measure of the solute's response to the reaction field of the solvent. In particular, we compare these quantities for the generalized Born model as implemented in the SM5.42R method, the multipolar expansion model developed at Nancy, and the MST version of the polarizable continuum model. All calculations are carried out at the HF/6-31G(d) level. The effects of various choices of solute cavities and representations of the charge density are examined. The test set consists of 18 molecules containing prototypical polar groups, and three different values of the dielectric permittivity are considered.
Accurate determination of absolute solvation free energy plays a critical role in numerous areas of biomolecular modeling and drug discovery. A quantitative representation of ligand and receptor desolvation, in particular, is an essential component of current docking and scoring methods. Furthermore, the partitioning of a drug between aqueous and nonpolar solvents is one of the important factors considered in pharmacokinetics. In this study, the absolute hydration free energy for a set of 239 neutral ligands spanning diverse chemical functional groups commonly found in drugs and drug-like candidates is calculated using the molecular dynamics free energy perturbation method (FEP/MD) with explicit water molecules, and compared to experimental data as well as its counterparts obtained using implicit solvent models. The hydration free energies are calculated from explicit solvent simulations using a staged FEP procedure permitting a separation of the total free energy into polar and nonpolar contributions. The nonpolar component is further decomposed into attractive (dispersive) and repulsive (cavity) components using the Weeks-Chandler-Anderson (WCA) separation scheme. To increase the computational efficiency, all of the FEP/MD simulations are generated using a mixed explicit/implicit solvent scheme with a relatively small number of explicit TIP3P water molecules, in which the influence of the remaining bulk is incorporated via the spherical solvent boundary potential (SSBP). The performances of two fixed-charge force fields designed for small organic molecules, the General Amber force field (GAFF), and the all-atom CHARMm-MSI, are compared. Because of the crucial role of electrostatics in solvation free energy, the results from various commonly used charge generation models based on the semiempirical (AM1-BCC) and QM calculations [charge fitting using ChelpG and RESP] are compared. In addition, the solvation free energies of the test set are also calculated using Poisson-Boltzmann (PB) and Generalized Born model of solvation (GB), which are two widely used continuum electrostatic implicit solvent models. The protocol for running the absolute solvation free energy calculations used throughout is automated as much as possible, with minimum user intervention, so that it can be used in large-scale analysis and force field optimization. Figure 2. Average unsigned error [AUE] in the absolute solvation free energies. The AUE is shown in the y-axis, and the chemical functionalities in the small molecules are plotted in the x-axis. The solid bars represent the solvation free energies calculated using explicit solvent/FEP method in CHARMM. The bars with dotted line and stripes represent the solvation free energy calculated using GB and PB model in Amber9.
Chemical Physics, 1993
The dispersion-repulsion contributions to the solvation energy, computed with surface integrals and uniform approxrmation for some hydrocarbons in water and methanol, are compared with the results obtained using more realistic solvent distribution functions from RISM integral equation. The cavity surface we use is not spherical and models the structure of the enclosed solute molecule through a set of interlocking spheres centered on the interaction gtes. The RXSM radial distribution functions are used to fix the value of the radii of closest approach between solute-&vent interaction centers that define a minimal cavity surface. Two ways of working with this approximation are examined comparing also local contributions on the cavity surface. It is possible to find a set of cavity radii, to be used in the uniform approximation, that lead to dispersion-repulsion contributions in good agreement with those derived from RISM radial distribution functions and show a satisfactory degree of transferability.
Physical Review E, 2002
In the density functional theory formulation of molecular solvents, the solvation free energy of a solute can be obtained directly by minimization of a functional, instead of the thermodynamic integration scheme necessary when using atomistic simulations. In the homogeneous reference fluid approximation, the expression of the free-energy functional relies on the direct correlation function of the pure solvent. To obtain that function as exactly as possible for a given atomistic solvent model, we propose the following approach: first to perform molecular simulations of the homogeneous solvent and compute the position and angle-dependent two-body distribution functions, and then to invert the Ornstein-Zernike relation using a finite rotational invariant basis set to get the corresponding direct correlation function. This rather natural scheme is proved, for the first time to our knowledge, to be valuable for a dipolar solvent involving long range interactions. The resulting solvent free-energy functional can then be minimized on a three-dimensional grid around a solute to get the solvent particle and polarization density profiles and solvation free energies. The viability of this approach is proven in a comparison with ''exact'' molecular dynamics calculations for the simple test case of spherical ions in a dipolar solvent.
Chemical Physics, 1993
A configuration interaction (CI) version of the self-consistent reaction field theory is formulated in order to treat solvation problems in the framework of the continuum medium model. The problem of an optimal selection of the truncated conligurational basis set for large molecular solutes is considered. For the description of solvation effects most important are found to be the charge transfer electronic configurations which can be treated on the background of incompletely convergent total CI expansions because the contributions of local excitations are mutually canceled with a high accuracy under the conditions of a solvent effect calculation.
Studies on free energy calculations. II. A theoretical approach to molecular solvation
The Journal of Chemical Physics, 1994
Using'the concepts of scaled particle theory, an analytical theory is developed to investigate the limiting behavior of solvation free energies at the particle creation limit. The new theory directly incorporates the weakly attractive, dispersion interaction terms into the analytical calculations. For neutral molecular systems, the effects of longer ranged electrostatic interactions are also incorporated, albeit in an ad hoc way, and the validity of the utilized assumptions are then demonstrated with numerical examples. It is shown that it is possible to blend the numerical and analytical methods to increase the reliability of quantitative results, and, at the same time, to achieve savings on computational expenditure for certain types of calculations. Different methods of performing the thermodynamic integration in solvation free energy calculations are also compared. Studied examples clearly show the importance of proper treatment of the divergence at the particle creation limit in obtaining quantitatively reliable results for the solvation free energies. 6126
New Implicit Solvation Models for Dispersion and Exchange Energies
The Journal of Physical Chemistry A, 2013
Implicit solvation models provide a very efficient means to estimate solvation energies. For example, dielectric continuum models are commonly used to obtain the long-range electrostatic interactions. These may be parametrized to also include in some average manner short-range interactions such as dispersion and exchange, but it is preferable to instead develop additional implicit models specifically designed for the shortrange interactions. This work proposes new models for dispersion and exchange interactions between solute and solvent by adapting approaches previously developed for treatment of gas-phase intermolecular forces. The new models are formulated in terms of the charge densities of the solutes and use only three adjustable parameters. To illustrate the performance of the models, electronic structure calculations are reported for a large number of solutes in two nonpolar solvents where short-range interactions dominate and different balances pertain between attractive dispersion and repulsive exchange contributions. After empirical optimization of the requisite parameters, it is found that the errors compared to experimental solvation free energies are only about 0.4 kcal/mol on average, which is better than previous approaches in the literature that invoke many more parameters.
The Journal of Chemical Physics, 2012
Integral equation theory for molecular liquids is one of the powerful frameworks to evaluate solvation free energy (SFE). Different from molecular simulation methods, the theory computes SFE in an analytical manner. In particular, the correction method proposed by Kovalenko and Hirata [Chem. Phys. Lett. 290, 237 (1998); Kovalenko and Hirata J. Chem. Phys. 113, 2793 (2000)]10.1063/1.1305885 is quite efficient in the accurate evaluation of SFE. However, the application has been limited to aqueous solution systems. In the present study, an improved method is proposed that is applicable to a wide range of solution systems. The SFE of a variety of solute molecules in chloroform and benzene solvents is evaluated. A key is the adequate treatment of excluded volume in SFE calculation. By utilizing the information of chemical bonds in the solvent molecule, the accurate computation of SFE is achieved.