Vacuum simulation

By using an effective, distance-dependent dielectric constant, the ability of bulk water to reduce electrostatic interactions can be mimicked without the presence of explicit solvent molecules. One disadvantage of aU vacuum simulations, corrected for shielding effects or not, is the fact that they cannot account for the ability of water molecules to form hydrogen bonds with charged and polar surface residues of a protein. As a result, adjacent polar side chains interact with each other and not with the solvent, thus introducing additional errors. 

Figure 3 Anharmonicity factor versus quasi-harmomc mode number from a 200 ps vacuum simulation of BPTI. It can be seen that beyond about the 200th mode the anharmonicity factors are about 1.0, indicating harmomcity. Those below mode number 200 show progressively greater anharmonicity factors, indicating that they span a space within which energy barriers are crossed. A similar picture was found for a I ns simulation of human lysozyme m water [61]. (Adapted from Ref. II.)...

What is the relationship between a constant dielectric and a distance dependant dielectric for pseudo-vacuum simulations ... 

The presence of aqueous solvent was found to have little effect upon the mean structure of the pyranoid ring in these MD simulations, with only slight deviations in the time-averaged structure away from that observed in vacuum simulations or in the crystallographic diffraction experiments ( ). However, the presence of the solute had substantial effects upon the average "structuring" of the solvent. Figure 7 displays a pair distribution function g(r), defined as (27)... 

All of the simulation approaches, other than harmonic dynamics, include the basic elements that we have outlined. They differ in the equations of motion that are solved (Newton s equations, Langevin equations, etc.), the specific treatment of the solvent, and/or the procedures used to take account of the time scale associated with a particular process of interest (molecular dynamics, activated dynamics, etc.). For example, the first application of molecular dynamics to proteins considered the molecule in vacuum.15 These calculations, while ignoring solvent effects, provided key insights into the important role of flexibility in biological function. Many of the results described in Chapts. VI-VIII were obtained from such vacuum simulations. Because of the importance of the solvent to the structure and other properties of biomolecules, much effort is now concentrated on systems in which the macromolecule is surrounded by solvent or other many-body environments, such as a crystal. 

Values in parentheses from a vacuum simulation of 50 ps with a more recent (CHARMM 19) potential function (H. Yu and M. Karplus, unpublished results). 

Figure 43. Solvent effects on local protein motions. The normalized displacement autocorrelation functions are plotted versus time for residues near the active site in lysozyme. Vacuum simulation results are plotted as dashed lines and solvent simulation results are plotted as solid lines for (a) Trp-62 N 1 and (b) Asn-46 Cfl.

In the active-site simulations of lysozyme108 (this chapter, Sect. B.2 above) similar water networks that stabilize charged groups have been observed. To illustrate the dynamics of the formation of such networks, a sequence of stereo plots showing the formation and evolution of a stable pair of positively charged residues is displayed in Fig. 56. The pair consists of (NH2)+ moieties of Arg-61 and Arg-73. The solvated structure evolved from a conformation obtained in a vacuum simulation of lysozyme.108,192 The sequence of plots shows the formation of the water-bridged pair over a time period from t = 0 ps to t 8 ps, which followed dynamical equilibration of the solvent around the fixed vacuum structure of the protein. After 8 ps, the ion-pair structure is stable, but fluctuations in the pattern of hydrogen bonds do occur typical... 

For the range of Mach numbers considered, the exhaust jet has greatly expanded from the nozzle diameter, but still the mean free path of the typical rocket exhaust stream is, at most, of the order of magnitude of the rocket nozzle exit diameter. Since for a fixed temperature, the mean free path is proportional to the pressure, it is necessary to reduce the background pressure by one or more orders of magnitude to achieve vacuum simulation. This requires a reduction in the number of rebounding molecules by one or more orders of magnitude. 

After this first investigation of ring flexibility behaviour under vacuum simulations, and because of the suspected strong influence of water as an explicit solvent, a second study has been performed using the RdPCA approach (Fig. 11) based on our simulation in explicit solvent (charge set 1). 

In general, the gross features of the present solution study are in general agreement with previous vacuum simulations [3,4] and crystallographic structure data [10,15]. However, the present study does indicate that the relative movements of the protein can, in specific regions, be different in... 

There has been considerable discussion about whether or not solvent water causes an increase or a decrease in the fluctuations in the glycosidic torsional angles during MD simulations relative to what would be observed in vacuum simulations. It would appear that the answer to this question is somewhat force field dependent, since various simulations have produced contradictory results. Most disaccharide simulations... 

---