Discussion of method

It has been pointed out that use of implicit methods dampens the highest frequencies [100]. However, in many cases of protein motions fast fluctuations in the dynamics are unimportant because they proceed on a time scale faster than the process of interest. This is the case of the gating mechanism of enzymes or ion channels [13, p.18]. In these cases, the use of implicit methods as in the reaction path method of Elber and coworkers has been quite successful. MUSICO can be seen as an alternative to this method. It is more applicable, since it does not require initial and final configurations, and thus can be applied to problems like protein folding.