Ions and the Protein Surface Revisited: Extensive Molecular Dynamics Simulations and Analysis of Protein Structures in Alkali-Chloride Solutions

Abstract

Proteins interact with ions in various ways. The surface of proteins has an innate capability to bind ions, and is also influenced by the screening of the electrostatic potential owing to the presence of salts in the bulk solution. Alkali metal ions and chlorides interact with the protein surface, but such interactions are relatively weak and often transient. In this paper, computer simulations and analysis of protein structures are used to characterize the interactions between ions and the protein surface. The results show that the ion-binding properties of protein residues are highly variable. For example, alkali metal ions are more often associated with aspartate residues than with glutamates, whereas chlorides are most likely to be located near arginines. When comparing NaCl and KCl solutions, it was found that certain surface residues attract the anion more strongly in NaCl. This study demonstrates that proteinsalt interactions should be accounted for in the planning and execution of experiments and simulations involving proteins, particularly if subtle structural details are sought after.

Modulation of GPCRs by monovalent cations and anions

“…Additionally, anion and cation specificity was described for several biological systems, e.g. proteins or even enzymatic activity by experimental techniques and molecular simulations (Collins et al 2007;Yang et al 2010;Friedman 2011;Rembert et al 2012;Lo Nostro and Ninham 2012;Stepankova et al 2013). Thus, differences in interaction of monovalent cations with GPCRs in the allosteric binding site are expected.…”

On the Function and Fate of Chloride Ions in Amyloidogenic Self-Assembly of Insulin in an Acidic Environment: Salt-Induced Condensation of Fibrils

“…17,18 A recent computational study suggested preference of chloride ions for sites with particular positively charged side chains (arginines). 19 Hence, pH and dissolved salts affect the rate of amyloid formation and the thermodynamic stability of fibrils through both nonspecific and specific mechanisms. 20−22 Another interesting problem linking amyloidogenesis and electrostatics is polymorphism of fibrils.…”

Computer simulations of alkali-acetate solutions: Accuracy of the forcefields in difference concentrations

“…Instead, it may well be that the simulation protocol, which uses finite interaction cutoff was the source of this artifact. It can be expected that this would be less pronounced on the surface of proteins, when the acetates are more static and the Coulomb cage extends to a larger volume 3,15 .…”

“…At the very least, simulations of macromolecule-ion interactions should be realistic in physiological concentrations. Fortunately, ion concentrations do not seem to affect simulated protein structure and dynamics too much 3,4 , although they do affect local interactions.…”

“…In order to perform realistic simulations of proteins or peptides in solutions, it is important that the forcefield parameters account for the energetics of ions in electrolyte solutions and at the same time in solutions that contain proteins [14][15][16] . Alkali ions bind mostly to the carboxylates 3,4,15 . Hence, the ability to correctly account for interactions between the cations and carboxylates is important for coherence between experiments and simulations 17 .…”