As will be discussed in greater detail below, this is not always the case in simulation because of misbalances in the commonly applied potentials. ![]() At low-to-moderate salt concentrations and also at physiological salt concentrations, crystals of salt should dissolve in water. This is nontrivial, because the interactions of salt with salt, water with salt, and water with water are subtle and represent a balance of large electrostatic and dipole interactions, small additive van der Waals interactions, and large changes in entropy, among other interactions. (18-23) To properly model biological phenomena at the atomic level, an accurate treatment of the ions and solvent is crucial. (1-6) Water and ions also modulate biomolecular stability, dynamics, and folding, (7-17) and ions are important mediators of catalytic activity. ![]() Monovalent salts such as Na +, K +, and Cl − are critically important in regulating the homeostasis and electric potentials of cells, and monovalent ions serve as important building blocks of biomolecular structure by stabilizing proteins, lipids, and nucleic acids through both specific and nonspecific interactions. Salt and solvation are fundamental to chemistry, biology, and life. In addition to well reproducing the solution and crystal properties, the new ion parameters well reproduce binding energies of the ions to water and the radii of the first hydration shells. The ion parameters developed, optimized, and characterized were targeted for use with some of the most commonly used rigid and nonpolarizable water models, specifically TIP3P, TIP4P EW, and SPC/E. The optimization across the entire monovalent series avoids systematic deviations. ![]() This is the first effort that systematically scans across the Lennard-Jones space (well depth and radius) while balancing ion properties like LE and LC across all pair combinations of the alkali ions and halide ions. To validate and optimize the parameters, we calculated hydration free energies of the solvated ions and also lattice energies (LE) and lattice constants (LC) of alkali halide salt crystals. To provide a more appropriate balance, we reoptimized the parameters of the Lennard-Jones potential for the ions and specific choices of water models. The likely cause of the artifact in the AMBER parameters relates to the naive mixing of the Smith and Dang chloride parameters with AMBER-adapted Åqvist cation parameters. Our starting point centered on observations from long simulations of biomolecules in salt solution with the AMBER force fields where salt crystals formed well below their solubility limit. The applied methodology is general and can be extended to other ions and to polarizable force-field models. Although it has been clearly demonstrated that truly accurate treatments of ions will require inclusion of nonadditivity and polarizability (particularly with the anions) and ultimately even a quantum mechanical treatment, our goal was to simply push the limits of the additive treatments to see if a balanced model could be created. ![]() In this work, we describe our efforts to build better models of the monovalent ions within the pairwise Coulombic and 6-12 Lennard-Jones framework, where the models are tuned to balance crystal and solution properties in Ewald simulations with specific choices of well-known water models. At present, the best force fields for biomolecules employ a simple additive, nonpolarizable, and pairwise potential for atomic interaction. A good model needs to simultaneously reproduce many properties of ions, including their structure, dynamics, solvation, and moreover both the interactions of these ions with each other in the crystal and in solution and the interactions of ions with other molecules. To properly model ionic interaction and stability in atomistic simulations of biomolecular structure, dynamics, folding, catalysis, and function, an accurate model or representation of the monovalent ions is critically necessary. Alkali (Li +, Na +, K +, Rb +, and Cs +) and halide (F −, Cl −, Br −, and I −) ions play an important role in many biological phenomena, roles that range from stabilization of biomolecular structure, to influence on biomolecular dynamics, to key physiological influence on homeostasis and signaling.
0 Comments
Leave a Reply. |