How Well Does Poisson−Boltzmann Implicit Solvent Agree with Explicit Solvent? A Quantitative Analysis

Abstract

We have quantitatively studied the performance of a finite-difference Poisson-Boltzmann implicit solvent with respect to the TIP3P explicit solvent in a range of systems of biochemical interest. An overall agreement was found between the tested implicit and explicit solvents for hydrogen-bonding/salt-bridging dimers and peptide monomers and dimers of different conformations and different lengths. These comparative analyses also indicate a good transferability of empirically optimized parameters for the implicit solvent from small training molecules to large testing peptides. However, deviations between the two tested solvents are also apparent. Specifically, a consistent deviation was observed when hydrogen-bonding or salt-bridging dimers are within 4-6 A. The deviation reaches a maximum at about 5.5 A, the so-called water-bridging distance. The tested implicit solvent, even with optimized parameters, cannot capture the subtle fluctuation in the distance-dependent reaction field energy profiles, although smoothed profiles can still be obtained and are in overall agreement with those in the explicit solvent. Interestingly, the same mechanism underlining the above discrepancy is also responsible for the larger deviations of certain peptide conformations, such as parallel beta-strand dimers. It is likely that the observed discrepancy may cause improper conformational distributions in simulations with the implicit solvent when hydrogen-bonding or salt-bridging interactions are crucial, such as secondary structure populations in proteins. Validation of the implicit solvent with optimized parameters in dynamics simulations will be the next step to study the influences of the observed discrepancy at biological conditions.

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

“…25 In order to test this idea, we systematically modified the hydrogen-bonding network of water around a methanol dimer by varying the intermonomer distance from 2 to 8 Å (Figure 2(a)). The dip in the polar solvation free energy at a distance of 4 Å (Figure 2(a), inset), indicates cooperative localization (bridging) of water molecules, [65][66][67] and con- firms a marked alteration of the hydrogen-bonding network. Nonetheless, the nonlinearity of the solvation response is essentially constant as a function of the separation distance (α = 0.76 ± 0.02); and analogous results are found for a formaldehyde dimer (Figure 2(b); α = 0.88 ± 0.01).…”

Prediction of SAMPL-1 Hydration Free Energies Using a Continuum Electrostatics-Dispersion Model

“…Additional terms may also need to be included to describe solute-solvent interactions that are currently poorly represented in the model; for example, directional effects in hydrogen bonding. 10 This may reduce the observed overestimation that is apparently due to an overly additive contribution of the dispersion term in the case of densely polar, hydrogen-bond-capable compounds, such as the major outliers highlighted earlier. A major benefit of the distinct hydration data set from the SAMPL-1 blind prediction challenge is that it highlights shortcomings of our current solvent model that need to be improved upon.…”

“…Over the years, much effort has been expended in developing and parametrizing solvation models at various levels of theory. [4][5][6][7][8][9][10] These invariably involve the use of published data sets of vacuum-to-water transfer free energies of small molecules that are divided into training and validation subsets. Experimental data are available for a few hundreds of small organic molecules.…”

Calculations of the second virial coefficients of protein solutions with an extended fast multipole method

“…(37) and (38), then the right-hand side vectors in Eqs. (41) and (42) and (42). The new solution ϕ is the sum of the one-body solution and the perturbation solutions from Eqs.…”