Biomolecular electrostatics and solvation: a computational perspective

Abstract

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

Figure 1

Water structure and average dipole moment around a K+ ion. The radial distribution function (RDF) of O…K+ and water dipole moment were computed from molecular dynamic simulations of K+ in water using a polarizable potential (Grossfield et al., 2003; Ren & Ponder, 2003). Note that the average dipole moment of the water in the first solvation shell is roughly similar to that of bulk water.

Figure 2

The reorientation and polarization response of water upon the insertion of a cation (K+) into the bulk water. The yellow vector on each water molecule represents the net induced dipole moment because of the electric field of the ion and other water molecules. The white vector is the permanent (gas-phase) dipole moments (1.8 D) of the water molecule. The average dipole moment of a water molecule in liquid is 2.6–3.0 D according to various theoretical calculations. The snapshot is taken from molecular dynamics simulations of K+ in water using the AMOEBA potential (Ren & Ponder, 2003).

Figure 3

This figure represents the solute-solvent site-site pair correlation functions g_uv(r) as a function of the separation distance r predicted by 1DRISM for N-Methyl Acetamide immersed in water at infinite dilution. For instance, g_NO(r) is the pair correlation function for a nitrogen atom in N-Methyl Acetamide molecule and an oxygen atom in water molecule

Figure 4

Images of the varying definitions for the biomolecular surface of fasciculin-2 (PDB ID: 1FAS) with electrostatic potential shown ranging from −5 kT/e (dark red) to +5 kT/e (dark blue). A. van der Waals surface. B. Solvent-excluded, molecular, or Connolly surface. C. Solvent-accessible surface.