We learned early in the computer study of the H-function with particle dynamics that the velocity distribution reaches a local equilibrium (Maxwellian) distribution fast, within a few mean collision times, but that the subsequent structural rearrangement of the particles can be quite slow, particularly if a highly correlated event of many degrees of freedom is involved. During that process potential energy is slowly converted into kinetic energy to reach overall equilibrium. To study processes that are so unlikely that they do not occur within long computer runs (typically less than 10 −8 s of real time) we developed a rare event algorithm. In that calculation the particles are brought adiabatically, that is so slowly that the system is at equilibrium in the presence of the external force at every step, to the rare event configuration (the activated state) and the work to do that is determined. The probability of the event is then calculated by standard reaction rate theory by also determining the transmission coefficient through releasing the constraint near the activated state and observing how often the system goes to the new state relative to how often it falls back to the initial state. The problem with that calculation besides the assumption of adiabaticity is that one needs a model for the activated state, which is often hard to guess. Simulated annealing might aid in the search for an activated state. The other possibility is to speed up particle dynamics and that can be done by direct simulation Monte Carlo, a stochastic particle solution of the Boltzmann equation for a perfect gas. That approach can be extended to higher densities, but the stochastic approach cannot account for the structural features of the medium. However, systems can be followed up to 10 −5 s . We have been able to follow, for example, droplet formation and coalescence by this method. To study even larger systems we have embedded this particle algorithm into a continuum Navier–Stokes algorithm to study the onset of hydrodynamic instabilities. However, the approach cannot deal with the protein folding problem, because the structural aspects dominate the process. One would have to embed molecular dynamics into a continuum, a much more computer intensive problem, in order to even treat water, for example, as a continuum beyond a few molecular layers around a biological molecule.
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