Basic strategies, timescales, and limitations
Key biomolecular events – such as conformational changes, folding, and binding – that are challenging to study using straightforward simulation may be amenable to study using “path sampling” methods. But there are a few things you should think about before getting started on path sampling. There are fairly generic features and limitations that govern all the path sampling methods I’m aware of.
Path sampling refers to a large family of methods that, rather than having the goal of generating an ensemble of system configurations, attempt to generate an ensemble of dynamical trajectories. Here we are talking about trajectory ensembles that are precisely defined in statistical mechanics. As we have noted in another post, there are different kinds of trajectory ensembles – most importantly, the equilibrium ensemble, non-equilibrium steady states, and the initialized ensemble which will relax to steady state. Typically, one wants to generate trajectories exhibiting events of interest – e.g., binding, folding, conformational change.