Adaptive sampling is a technique used in computational molecular biology to efficiently simulate protein folding when coupled with molecular dynamics simulations.
Proteins spend a large portion – nearly 96% in some cases[1] – of their folding time "waiting" in various thermodynamic free energy minima. Consequently, a straightforward simulation of this process would spend a great deal of computation to this state, with the transitions between the states – the aspects of protein folding of greater scientific interest – taking place only rarely.[2] Adaptive sampling exploits this property to simulate the protein's phase space in between these states. Using adaptive sampling, molecular simulations that previously would have taken decades can be performed in a matter of weeks.[3]
If a protein folds through the metastable states A -> B -> C, researchers can calculate the length of the transition time between A and C by simulating the A -> B transition and the B -> C transition. The protein may fold through alternative routes which may overlap in part with the A -> B -> C pathway. Decomposing the problem in this manner is efficient because each step can be simulated in parallel.[3]
Adaptive sampling is used by the Folding@home distributed computing project in combination with Markov state models.[2][3]
While adaptive sampling is useful for short simulations, longer trajectories may be more helpful for certain types of biochemical problems.[4][5]