Solvation simulation length

M. R. Reddy and M. D. Erion, J. Comput. Chem., 20,1018 (1999), Calculation of Relative Solvation Free Energy Differences by Thermodynamic Perturbation Method Dependence of the Free Energy Results on the Simulation Length. 

It is clear that the ensemble averages in equation (2) can be estimated from molecular dynamics simulations. Calculations along these lines began shortly after simulations on proteins became feasible, but only recently have systematic solvated simulations of useful length become accessible. These can be directly compared to experimental data (as a check on the quality of the force fields and simulation methods), and can also be used to help decide which approximate models are most appropriate. It is customary to compute from the simulation a normalized time-correlation function. 

Of course, concerns about periodicity only relate to systems that are not periodic. The discussion above pertains primarily to the simulations of liquids, or solutes in liquid solutions, where PBCs are a useful approximation that helps to model solvation phenomena more realistically than would be the case for a small cluster. If the system truly is periodic, e.g., a zeolite crystal, tlien PBCs are integral to the model. Moreover, imposing PBCs can provide certain advantages in a simulation. For instance, Ewald summation, which accounts for electrostatic interactions to infinite length as discussed in Chapter 2, can only be carried out within the context of PBCs. 

When two such surfaces approach each other, layer after layer is squeezed out of the closing gap (Fig. 6.12). Density fluctuations and the specific interactions then cause an exponentially decaying periodic force the periodic length corresponds to the thickness of each layer. Such forces were termed solvation forces because they are a consequence of the adsorption of solvent molecules to solid surfaces [168], Periodic solvation forces across confined liquids were first predicted by computer simulations and theory [168-171], In this case, however, the experimental proof came only few years afterwards using the surface forces apparatus [172,173]. Solvation forces are not only an important factor in the stability of dispersions. They are also important for analyzing the structure of confined liquids. 

The simplest solution to increase the sampling of biomolecular systems is to perform longer simulations. Ten years ago, the time scale accessible for peptide simulation in explicit solvent was on the order of 100 ps [37, 38]. Today simulations of this length are routinely used in structural refinement and modelling studies. At present, about 1 s of CPU time on a fast processor is required to compute 1 fs of an MD trajectory of a small biomolecular system in aqueous solution with a total of 5000 atoms. This means that about one day on one processor is required to compute a 100 ps MD trajectory for such a system. However, about one year on 300 processors is required to compute a 1 is MD trajectory for such a system. Thus, the maximum accessible time scale is usually on the order of 100 ns for solvated biomolecules [39, 40]. 

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