The Dipolar Solvent Model and Its Applications to the Structural Analysis of Low-(SAXS) and High-(CRYSTALLOGRAPHY) Resolution X-Ray Data

Abstract

The Poisson-Boltzmann (PB) formalism is one of the most popular approaches to modeling the solvation of molecules. It assumes a continuum model for water, leading to a dielectric permittivity that depends on regions of space (inside or outside the solute). In contrast, the dipolar Poisson-Boltzmann-Langevin (DPBL) formalism follows a grid-based approach where the solvent is represented as a collection of freely orientable dipoles with nonuniform concentration [1]. This leads to a nonlinear permittivity function that depends both on the position and on the local electric field at that position. In practice, solving the modified PB equation in the DPBL formalism yields density maps for water (dipoles) and salt (ions). We illustrate here how these maps can be used to help in the analysis of both low- and high-resolution structural X-ray data. As for the former, we implemented a program, AquaSAXS [2], available as a web server, which uses the solvent density map to represent the hydration layer of a given protein atomic model. This approach improves the model where the hydration layer is defined as a constant layer on the surface. As for the latter, we will present how this approach is suited for electrostatics studies of solvation in confined geometries. In particular, its application to the study of pentameric ligand-gated ion channels helped proposing a plausible ion permeation mechanism [3].[1] Koehl and Delarue (2010) J Chem Phys 132(6) - 064101.[2] Poitevin et al (2011) NAR 39 - W184-9.[3] Sauguet, Poitevin, Murail et al (2013) EMBO J 32(5) - 728-41.