Global Influences on the Structure and Motional Amplitudes

To illustrate the solvent effect on the average structure of a protein, we describe results obtained from conventional molecular dynamics simulations with periodic boundary conditions.92,193 This method is well suited for a study of the global features of the structure for which other approaches, such as stochastic boundary simulation methods, would not be appropriate. We consider the bovine pancreatic trypsin inhibitor (BPTI) in solution and in a crystalline environment. A simulation was carried out for a period of 25 ps in the presence of a bath of about 2500 van der Waals particles with a radius and well depth corresponding to that of the oxygen atom in ST2 water.193 The crystal simulation made use of a static crystal environment arising from the surrounding protein molecules in the absence of solvent. These studies, which were the first application of simulation methods to determine the effect of the environment on a protein, used simplified representations of the surround- 

With the availability of faster computers, BPTI was simulated in aqueous solution and in a solvated crystal with a more realistic (three-center) water model.92 The simulations were limited to 8 ps of equilibration and 12 ps of analysis, somewhat short for definitive conclusions to be drawn recently, a crystal simulation of BPTI that extended over 40 ps has been reported.322 The average structures obtained from the various simulations are compared in Table VII. In the three calculations made with the same empirical potential, the van der Waals solvent and static crystal field results yielded an average structure closer to the experimental crystal structure than did the vacuum calculation. The full crystal simulations, including crystal waters, gave an average structure still closer to the X-ray result, while the deviation from the crystal structure of the average structure obtained from the aqueous solution simulation was similar to the earlier vacuum result. 

One difficulty with the above comparisons is that different empirical en- 

In summary, the molecular dynamics simulations show that the net effect of solvent on the overall structure of a protein is rather small and that the structure in the crystal is similar to that obtained in solution. This point is of some relevance since X-ray studies of the crystalline state are the basis for much of our current understanding of the structure and function of proteins. 

Effects of Solvent and Crystalline Environment on the Root-Mean-Square Fluctuations, Ar2 l/2 in A, of atoms in BPTI  

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