Solvent reaction field potential inside an uncharged globular protein: A bridge between implicit and explicit solvent models?

Abstract

The solvent reaction field potential of an uncharged protein immersed in Simple Point Charge/ Extended (SPC/E) explicit solvent was computed over a series of molecular dynamics trajectories, intotal 1560 ns of simulation time. A finite, positive potential of 13 to 24 k b Te c −1 (where T = 300K), dependent on the geometry of the solvent-accessible surface, was observed inside the biomolecule. The primary contribution to this potential arose from a layer of positive charge density 1.0 Å from the solute surface, on average 0.008 e c /Å 3 , which we found to be the product of a highly ordered first solvation shell. Significant second solvation shell effects, including additional layers of charge density and a slight decrease in the short-range solvent-solvent interaction strength, were also observed. The impact of these findings on implicit solvent models was assessed by running similar explicit-solvent simulations on the fully charged protein system. When the energy due to the solvent reaction field in the uncharged system is accounted for, correlation between per-atom electrostatic energies for the explicit solvent model and a simple implicit (Poisson) calculation is 0.97, and correlation between per-atom energies for the explicit solvent model and a previously published, optimized Poisson model is 0.99.

Rapid Prediction of Solvation Free Energy. 2. The First-Shell Hydration (FiSH) Continuum Model

“…In fact, for a convex solute, a slightly larger Born radius than the van der Waals radius may be expected because the hydrogen density from the first shell of waters would be located at a slightly greater distance from the surface than the oxygen density. This effect is especially pronounced for small spherical solutes, but still present around an uncharged protein using long MD simulations in SPC/E water 41 where hydrogen densities were 0.1 Å further away from the protein than peak oxygen densities for the first solvation shell. Also, interpolation of our data on varying the size of spherical solutes ( Figure 2B) suggests slightly larger increases of Born radii for the uncharged spheres with smaller van der Waals radii (i.e., more convex).…”

On the origin of the electrostatic potential difference at a liquid-vacuum interface

“…Recent studies have measured a nonzero potential within an uncharged LJ solute due to the surrounding solvent. [39][40][41] This is the solute-solvent interface potential. Including these contributions into the solvation free energy, yields…”

Electrostatics in Proteins and Protein–Ligand Complexes

“…Water molecules bound to the charged surface residues have been suggested recently to behave more like extensions of the solute rather than mobile bulk waters [23,24]. This is particularly the case with internal waters which can bridge electrostatic interactions between solute atoms and, thus, play a prominent role in enzyme catalysis and ligand binding [25,26].…”