Some challenges of diffused interfaces in implicit-solvent models

TL;DR

This paper investigates the effects of diffuse interface shapes on solvation and binding energies in implicit-solvent models, proposing a coupled FEM-BEM approach and analyzing parameter sensitivities.

Contribution

It introduces a coupled FEM-BEM scheme to analyze diffuse interface effects on electrostatic calculations, highlighting the impact of interface shape parameters.

Findings

High $k_p$ values increase interface gradients, approaching sharp interfaces.

Optimal $k_p$ for solvation energies is around 3.

Binding energies are highly sensitive to small variations in $k_p$, with optimal values ranging from 2 to 20.

Abstract

The standard Poisson-Boltzmann model for molecular electrostatics assumes a sharp variation of the permittivity and salt concentration along the solute-solvent interface. The discontinuous field parameters are not only difficult numerically, but also are not a realistic physical picture, as it forces the dielectric constant and ionic strength of bulk in the near-solute region. An alternative to alleviate some of these issues is to represent the molecular surface as a diffuse interface, however, this also presents challenges. In this work we analysed the impact of the shape of the interfacial variation of the field parameters in solvation and binding energy. However we used a hyperbolic tangent function ($\tanh(k_p x)$) to couple the internal and external regions, our analysis is valid for other definitions. Our methodology was based on a coupled finite element (FEM) and boundary element (BEM) scheme that allowed us to have a special treatment of the permittivity and ionic strength in a bounded FEM region near the interface, while maintaining BEM elsewhere. Our results suggest that the shape of the function (represented by $k_p$) has a large impact on solvation and binding energy. We saw that high values of $k_p$ induce a high gradient on the interface, to the limit of recovering the sharp jump when $k_p\to\infty$, presenting a numerical challenge where careful meshing is key. Using the FreeSolv database to compare with molecular dynamics, our calculations indicate that an optimal value of $k_p$ for solvation energies was around 3. However, more challenging binding free energy tests make this conclusion more difficult, as binding showed to be very sensitive to small variations of $k_p$. In that case, optimal values of $k_p$ ranged from 2 to 20.