On the modeling of polar component of solvation energy using smooth Gaussian-based dielectric function

Abstract

Traditional implicit methods for modeling electrostatics in biomolecules use a two-dielectric approach: a biomolecule is assigned low dielectric constant while the water phase is considered as a high dielectric constant medium. However, such an approach treats the biomolecule-water interface as a sharp dielectric border between two homogeneous dielectric media and does not account for inhomogeneous dielectric properties of the macromolecule as well. Recently we reported a new development, a smooth Gaussian-based dielectric function which treats the entire system, the solute and the water phase, as inhomogeneous dielectric medium (J Chem Theory Comput. 2013 Apr 9; 9(4): 2126-2136.). Here we examine various aspects of the modeling of polar solvation energy in such inhomogeneous systems in terms of the solute-water boundary and the inhomogeneity of the solute in the absence of water surrounding. The smooth Gaussian-based dielectric function is implemented in the DelPhi finite-difference program, and therefore the sensitivity of the results with respect to the grid parameters is investigated, and it is shown that the calculated polar solvation energy is almost grid independent. Furthermore, the results are compared with the standard two-media model and it is demonstrated that on average, the standard method overestimates the magnitude of the polar solvation energy by a factor 2.5. Lastly, the possibility of the solute to have local dielectric constant larger than of a bulk water is investigated in a benchmarking test against experimentally determined set of pKa's and it is speculated that side chain rearrangements could result in local dielectric constant larger than 80.

DelPhi Suite: New Developments and Review of Functionalities

“…Instead we would like to consider that there is a smooth transition between macromolecule and water phase. Thus, in the Gaussian‐based approach atom, densities are presented as Gaussian density function . Then using the resulting density function, one delivers the dielectric “constant” as a function of space (details are provided in the corresponding references) (Supporting Information Fig.…”

Continuum Electrostatics Approaches to Calculating pKas and Ems in Proteins

“…To address this issue, Knapp has explored the effects of modeling the cavities with higher detail using a finer grid, which can accept smaller or less spherical wet regions, which improves the fit to benchmark p K a s (Meyer, Kieseritzky & Knapp, 2011). Other methods make use of Gaussian dielectric boundaries in the calculation of the Poisson-Boltzmann equation, which also raises the effective internal dielectric constant (Word & Nicholls, 2011; Li, Li & Alexov, 2014). …”

Breaking the polar‐nonpolar division in solvation free energy prediction

“…The most popular implicit solvent model is based on the Poisson–Boltzmann (PB) theory, which retains an atomistic description of the solute molecule, while treating the solvent and includes possible ions and cofactors as a dielectric continuum . More recently, Gaussian‐based smooth dielectric functions have also shown success for computing solvation energy of both small molecules and proteins . The PB model is generally accepted to be one of the most accurate implicit solvent models.…”

“…[23][24][25][26][27][28] More recently, Gaussian-based smooth dielectric functions have also shown success for computing solvation energy of both small molecules and proteins. [29,30] The PB model is generally accepted to be one of the most accurate implicit solvent models. In fact, it can be combined with the density functional theory (DFT) for a more accurate description of solvent polarization and solute response.…”