Electrostatic simulations, hydration

The second necessary ingredient in the primitive quasichemical formulation is the excess chemical potential of the metal-water clusters and of water by itself. These quantities p Wm — can typically be obtained from widely available computational packages for molecular simulation [52], In hydration problems where electrostatic interactions dominate, dielectric models of those hydration free energies are usually satisfactory. The combination /t xWm — m//, wx is typically insensitive to computational approximations because the water molecules coat the surface of the awm complex, and computational errors can compensate between the bound and free ligands. 

This electrostatic embedding strategy has been successfully applied in a variety of QMCF MD simulations of hydrated systems (38 3). The embedding technique in connection with improvements of the QM/MM coupling leads to a significantly increased accuracy of the description of the systems compared to conventional QM/MM MD procedures. The QMCF framework is compatible with any affordable quantum chemical level and will enable the application of correlated ab initio methods (e.g., MP/2) in the near future. 

The influence of a cut-off relative to the full treatment of electrostatic interactions by Ewald summation on various water parameters has been investigated by Feller et al. [33], These authors performed simulations of pure water and water-DPPC bilayers and also compared the effect of different truncation methods. In the simulations with Ewald summation, the water polarization profiles were in excellent agreement with experimental values from determinations of the hydration force, while they were significantly higher when a cut-off was employed. In addition, the calculated electrostatic potential profile across the bilayer was in much better agreement with experimental values in case of infinite cut-off. However, the values of surface tension and diffusion coefficient of pure water deviated from experiment in the simulations with Ewald summation, pointing out the necessity to reparameterize the water model for use with Ewald summation. 

Previous studies have shown that there is a correlation between the enthalpy of hydration of alkanes and their accessible surface area [30,31] or related magnitudes. Moreover, relationships between the hydration numbers calculated from discrete simulations for hydrocarbons and both the free energy and enthalpy of hydration of these molecules have also been reported [32] and have been often used to evaluate solvation enthalpies. Analysis of our results, illustrates the existence of a linear relationship between A//n eie and the surface of the van der Waals cavity,. SVw, defined in MST computations for the calculation of the non-electrostatic contributions (Figure 4-1). In contrast, no relationship was found for the electrostatic component of the hydration enthalpy (A//eie data not shown). Clearly, in a first approximation, one can assume that the electrostatic interactions between solute and solvent can be decoupled from the interactions formed between uncharged solutes and solvent molecules. 

The most expensive part of a simulation of a system with explicit solvent is the computation of the long-range interactions because this scales as Consequently, a model that represents the solvent properties implicitly will considerably reduce the number of degrees of freedom of the system and thus also the computational cost. A variety of implicit water models has been developed for molecular simulations [56-60]. Explicit solvent can be replaced by a dipole-lattice model representation [60] or a continuum Poisson-Boltzmann approach [61], or less accurately, by a generalised Bom (GB) method [62] or semi-empirical model based on solvent accessible surface area [59]. Thermodynamic properties can often be well represented by such models, but dynamic properties suffer from the implicit representation. The molecular nature of the first hydration shell is important for some systems, and consequently, mixed models have been proposed, in which the solute is immersed in an explicit solvent sphere or shell surrounded by an implicit solvent continuum. A boundary potential is added that takes into account the influence of the van der Waals and the electrostatic interactions [63-67]. 

Zauhar, R. (1991). The incorporation of hydration forces determined by continuum electrostatics into molecular mechanics simulations. J. Comp. Chem. 12 575-583. 

We summarise recent work on computer modelling and simulation of proteins involved in bioenergetic processes and in peptide-membrane interactions. Homology modelling, electrostatic calculations and conformational analysis of a photosynthetic reaction centre protein are described. Bacteriorhodopsin, a light-driven proton pump protein is examined from several aspects, including its hydration and conformational thermodynamics. Finally, we present results on lipid perturbation on interaction with a cyclic decapeptide antibiotic, gramicidin S. 

Deng, Y., Roux, B. Hydration of amino add side chains Nonpolar and electrostatic contributions calculated from staged molecular dynamics free energy simulations with explicit water molecules, J. Chem. Phys. 2004,108,16567-76. 

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