Restoring Charge Asymmetry in Continuum Electrostatics Calculations of Hydration Free Energies

Abstract

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Rapid Prediction of Solvation Free Energy. 2. The First-Shell Hydration (FiSH) Continuum Model

“…51 In the case of the linear function in eq 3, initial values for the c + and c -parameters were taken from our previous fitting to hexagonal neutral bracelets as model compounds. 23 Other Continuum Solvation Models. The transferability of the FiSH model will be assessed by comparison to previously developed continuum solvation models, a continuum electrostatics-dispersion (CED) model and a continuum model consisting of only reaction field electrostatics (RF), both of which have been developed and used previously.…”

“…23 In this approach, we used the average induced surface charge density (ISCD), σ i , obtained from a boundary element solution of the Poisson equation to derive a simple linear correction to the van der Waals radius to obtain the Born radius, r i Born , for each atom, i, of a molecule. 23 To obtain the σ i for eq 3, all atoms are initially assigned Born radii equal to the General AMBER Force Field (GAFF) 39 van der Waals radii r i 0 . From the boundary element solution to the Poisson equation, the average ISCDs for each atom are then calculated by assigning the surface patches and their associated charge density to the nearest atom.…”

“…Thus, in this work, we retrained the continuum electrostatic coefficients, c + and c -,t ot h e explicit-solvent LIE electrostatic component for the training data set of 200 neutral molecules and obtained slightly different values of 16.222 Å 3 /e and 11.843 Å 3 /e for c + and c -, respectively, compared to the previous values of 15.5 Å 3 /e and 11.5 Å 3 /e. 23 The relatively small change in c + and c -coefficients in going from simple model systems to a 200-molecule training set suggests that the coefficients are not overly sensitive to the atom types, at least as far as neutral molecules go. It also suggests that the linear correction in eq 3 may perform relatively well for the normal range of partial charges observed in neutral real molecules.…”

“…We propose here the First-Shell Hydration (FiSH) model, a continuum solvation model that reformulates the usual continuum electrostatics and van der Waals treatments in order to capture features present in the all important first shell of hydration. 23 The FiSH continuum model is designed to mimic an explicit solvent LIE model of hydration. As in the companion study using explicit solvent LIE simulation, 24 the FiSH model is applied on a large hydration data set encompassing 501 "traditional" compounds 25,26 and 63 neutral drug-like compounds from the more challenging SAMPL1 data set.…”

The electrostatic response of water to neutral polar solutes: Implications for continuum solvent modeling

“…56,57 The atomic cavity radius of each solute atom, for a given value of λ, was set to the time-averaged mean distance from the atom's center to the nearest water oxygen in the corresponding explicit-water simulation, offset by a λ-independent constant designed to account for the asymmetry of the water molecule. 58,59 The offset was −0.84 Å for atoms having a positive charge in the fully charged (λ = 1) state, and −1.4 Å for atoms having a negative charge in the fully charged state. These offsets were established by fitting PB solvation free energies of methanol and formaldehyde against those computed using explicit-water molecular dynamics simulations.…”