Comparison of different schemes to treat long‐range electrostatic interactions in molecular dynamics simulations of a protein crystal

Abstract

Eight molecular dynamics simulations of a ubiquitin crystal unit cell were performed to investigate the effect of different schemes to treat the long-range electrostatic interactions as well as the need to include counter ions. A crystal system was chosen as the test system, because the higher charge density compared with a protein in solution makes it more sensitive to the way of treating the electrostatic interactions. Three different schemes of treating the long-range interactions were compared: straight cutoff, reaction-field approximation, and a lattice-sum method (P3M). For each of these schemes, two simulations were performed, one with and one without the counter ions. Two additional simulations with a reaction-field force and different initial placements of the counter ions were performed to examine the effect of the initial positions of the ions. The inclusion of long-range electrostatic interactions using either a reaction-field or a lattice-sum method proved to be necessary for the simulation of crystals. These two schemes did not differ much in their ability to reproduce the crystallographic structure. The inclusion of counter ions, on the other hand, seems not necessary for obtaining a stable simulation. The initial positions of the ions have a visible but small effect on the simulation.

Molecular dynamics simulations of potassium channels

“…In recent literature, studies dealing with the importance of accurately treating these interactions are reported in the context of structure and stability of membranes or membranes with inserted peptides and several groups have described artifacts linked with the choice of electrostatic treatment in biological applications [59,66,[71][72][73]. It is interesting to observe, that some controversy emerges from these studies and that there is an ongoing debate concerning possible artifacts arising from the use of these methods.…”

Diffusion of water and sodium counter-ions in nanopores of a β-lactoglobulin crystal: a molecular dynamics study

“…Consequently, simulated properties do not depend on the arbitrary initial placement of the ions [20]. Figures 6(a) and (b) show the displacements of 15 out of 40 sodium ions along the z-axis of the unit cell (see figure 1), as a function of time with and without protein restraints.…”

Effects of Temperature and Salt Concentration on the Structural Stability of Human Lymphotactin: Insights from Molecular Simulations

“…[27][28][29][30][31][32] The importance of salt on protein stability was also illustrated in several molecular dynamics simulations. 33,34 Although including counter ions for proteins with a low overall charge was shown not as important, 35 proteins with a higher overall charge are more sensitive to the ionic environment. For the highly charged βARK PH domain (+6 overall charge), for example, including ions to near physiological concentration was found necessary to stabilize the protein during simulation since otherwise there were not enough ions near the protein surface to screen the strong interactions among charged residues.…”