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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.

SUBMITTER: Li L

PROVIDER: S-EPMC4092036 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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On the Modeling of Polar Component of Solvation Energy using Smooth Gaussian-Based Dielectric Function.

Li Lin L Li Chuan C Alexov Emil E

Journal of theoretical & computational chemistry 20140501 3

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 smoo ...[more]

PMID: 25018579

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Project description:Calculations of electrostatic potential and solvation free energy of macromolecules are essential for understanding the mechanism of many biological processes. In the classical implicit solvent Poisson-Boltzmann (PB) model, the macromolecule and water are modeled as two-dielectric media with a sharp border. However, the dielectric property of interior cavities and ion-channels is difficult to model realistically in a two-dielectric setting. In fact, the detection of water molecules in a protein cavity remains to be an experimental challenge. This introduces an uncertainty, which affects the subsequent solvation free energy calculation. In order to compensate this uncertainty, a novel super-Gaussian dielectric PB model is introduced in this work, which devices an inhomogeneous dielectric distribution to represent the compactness of atoms and characterizes empty cavities via a gap dielectric value. Moreover, the minimal molecular surface level set function is adopted so that the dielectric profile remains to be smooth when the protein is transferred from water phase to vacuum. An important feature of this new model is that as the order of super-Gaussian function approaches the infinity, the dielectric distribution reduces to a piecewise constant of the two-dielectric model. Mathematically, an effective dielectric constant analysis is introduced in this work to benchmark the dielectric model and select optimal parameter values. Computationally, a pseudo-time alternative direction implicit (ADI) algorithm is utilized for solving the super-Gaussian PB equation, which is found to be unconditionally stable in a smooth dielectric setting. Solvation free energy calculation of a Kirkwood sphere and various proteins is carried out to validate the super-Gaussian model and ADI algorithm. One macromolecule with both water filled and empty cavities is employed to demonstrate how the cavity uncertainty in protein structure can be bypassed through dielectric modeling in biomolecular electrostatic analysis.

Dataset Information

On the Modeling of Polar Component of Solvation Energy using Smooth Gaussian-Based Dielectric Function.

Publications

On the Modeling of Polar Component of Solvation Energy using Smooth Gaussian-Based Dielectric Function.

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