Implicit Nonpolar Solvent Models

Abstract

We have systematically analyzed a new nonpolar solvent model that separates nonpolar solvation free energy into repulsive and attractive components. Our analysis shows that either molecular surfaces or volumes can be used to correlate with repulsive free energies of tested molecules in explicit solvent with correlation coefficients higher than 0.99. In addition, the attractive free energies in explicit solvent can also be reproduced with the new model with a correlation coefficient higher than 0.999. Given each component optimized, the new nonpolar solvent model is found to reproduce monomer nonpolar solvation free energies in explicit solvent very well. However, the overall accuracy of the nonpolar solvation free energies is lower than that of each component. In the more challenging dimer test cases, the agreement of the new model with explicit solvent is less impressive. Nevertheless, it is found that the new model works reasonably well for reproducing the relative nonpolar free energy landscapes near the global minimum of the dimer complexes.

Energetics and Dynamics Across the Bcl-2-Regulated Apoptotic Pathway Reveal Distinct Evolutionary Determinants of Specificity and Affinity

“…The chosen scheme for computing ΔGnonpolar yielded ΔH values which are of similar magnitude to calorimetric data ) (~ -10 to -25 kcal/mol), whereas the alternative scheme, where ΔGnonpolar is linearly dependent upon solvent accessible surface area, significantly overestimated ΔH (~ -80 to -100 kcal/mol). Our work, therefore, corroborates the benefit of decomposing ΔGnonpolar into a dispersive (attractive) and cavitation (repulsive) term (Tan et al, 2007).…”

Poisson–Boltzmann model analysis of binding mRNA cap analogues to the translation initiation factor eIF4E

“…However we should add that some consistent coupling of non polar and polar solvation free energies in the context of computation of the binding free energies is desired and such work is in progress [50]. It is also useful to point to recent important improvements in modelling non polar contributions to free energy of binding, particularly a recognition of non polar attractive and repulsive contributions to free energy of binding which must be modelled separately [51,52,53].…”

Modeling aqueous solvation with semi-explicit assembly

“…However, implicit models often require trade-offs in the physics that can limit their accuracies. For example, water is typically treated as a continuum rather than individual particles, and this neglects discrete microscopic effects; nonpolar solvation effects are often assumed to depend only on surface area A (expressed as γA), and not on detailed dispersive interactions and collective consequences of solute shape (18)(19)(20).It would be useful to have a computational model of water that is both fast-approaching the speeds of the fastest implicitsolvent models-and that captures the physics and the transferability of explicit-solvent models. Toward this goal, various improvements of implicit models have been introduced (21, 22), explicit solvents have been coarse-grained (23, 24), and hybrid explicit-implicit models have been developed (25)(26)(27)(28)(29).…”

“…However, implicit models often require trade-offs in the physics that can limit their accuracies. For example, water is typically treated as a continuum rather than individual particles, and this neglects discrete microscopic effects; nonpolar solvation effects are often assumed to depend only on surface area A (expressed as γA), and not on detailed dispersive interactions and collective consequences of solute shape (18)(19)(20).…”