Molecular dynamics of a protein surface: ion-residues interactions

Abstract

Time-resolved measurements indicated that protons could propagate on the surface of a protein or a membrane by a special mechanism that enhanced the shuttle of the proton toward a specific site. It was proposed that a suitable location of residues on the surface contributes to the proton shuttling function. In this study, this notion was further investigated by the use of molecular dynamics simulations, where Na(+) and Cl(-) are the ions under study, thus avoiding the necessity for quantum mechanical calculations. Molecular dynamics simulations were carried out using as a model a few Na(+) and Cl(-) ions enclosed in a fully hydrated simulation box with a small globular protein (the S6 of the bacterial ribosome). Three independent 10-ns-long simulations indicated that the ions and the protein's surface were in equilibrium, with rapid passage of the ions between the protein's surface and the bulk. However, it was noted that close to some domains the ions extended their duration near the surface, thus suggesting that the local electrostatic potential hindered their diffusion to the bulk. During the time frame in which the ions were detained next to the surface, they could rapidly shuttle between various attractor sites located under the electrostatic umbrella. Statistical analysis of the molecular dynamics and electrostatic potential/entropy consideration indicated that the detainment state is an energetic compromise between attractive forces and entropy of dilution. The similarity between the motion of free ions next to a protein and the proton transfer on the protein's surface are discussed.

FIGURE 1

The mean square deviations (MSD) of the Cl⁻ (A) and Na⁺ (B) ions as a function of simulation time, calculated over the simulation MD_N. The MSDs are given in nanometers squared and the time is given in nanoseconds.

FIGURE 2

The minimal distance, in nanometers, between any of the Cl⁻ (A); any of the Na⁺ ions (B); individual Cl⁻ ions (C; each of the four ions is colored differently) or individual Na⁺ ions, and the protein as a function of simulation time, calculated over the simulation MD_N. The distances in nanometers and the time is given in nanoseconds. The absolute minimal distance (∼0.2 nm) is dictated by the steric interferences between the van der Waals radii of the ions.

FIGURE 3

The distribution functions for the minimal distances between the Cl⁻ ions (black) or Na⁺ ions (gray) and the protein, in the simulations MD_N (A) and MD_S (B). The distances are given in nanometers. Only the main part of the distribution is shown.

FIGURE 4

The electrostatic potential surface around the protein. (A) Residue His-16 (which is transiently located in the vicinity of the ion) and the two attractor sites Glu-41 and Glu-95 are presented under the positive Coloumb cage umbrella. (B) Residues Arg-80 and Arg-87, which are the strongest ion attractors, and Lys-92, which is located in their vicinity and forms a weak ion attractor, are presented as the ion is detained by Arg-80 and Arg-87. The Coulomb cages for the positive (blue) and negative (red) domains are drawn at the distance where the electrostatic potential equals 1 k_BT/e.

FIGURE 5

The bound ions and their immediate vicinity. (A) A chloride ion bound to residues Arg-80, Arg-87, and Tyr-50. The minimal distances between the ion and the residues were 2.24, 2.86, and 2.02 Å for Arg-80, Arg-87, and Tyr-50, respectively. (B) A sodium ion bound to Glu-31. The minimal distance between the ion and the protein is 4.34 Å.

FIGURE 6

(A) The distance between one of the chloride ions and the hydrogen atoms attached to the guanido group of Arg-47 (gray) or to the amino group of Lys-54 (black), as a function of simulation time, during the simulation MD_N. The ion rapidly moves from the vicinity of Arg-47 to the vicinity of Lys-54. (B) The distance between one of the sodium ions and the carboxylate oxygens of Glu-31 (points), Glu-38 (solid line), and Glu-66 (gray) as a function of simulation time, during the simulation MD_N. The ion is first associated with Glu-38 and Glu-66 and then with Glu-31.