Ensemble
An ensemble (or alternatively statistical ensemble) is a concept from statistical mechanics. Specifically, an ensemble is the probability distribution of the state of a system.
==Conceptualizing Ensembles==
Understanding exactly what an ensemble is and why it is important may be easiest to grasp if we first imagine a macroscopic case study. Suppose I had two large buckets that were distinct from each other (for example, different colors). And suppose I had a certain number of apples (or any other object of your choice) that I wanted to split between the two buckets. Here, the ensemble would be collectively all of the different ways (or states) I could split the apples between the two buckets.
In this example, it is worth noting that the probability of observing a certain state (after the apples have been sorted) is not equal across all state. Assuming we have an impartial sorter (who has a 50% chance of putting a given apple into the first bucket and a 50% chance into the second bucket), we would intuitively expect to see a relatively equal number of apples in each bucket compared to, say, all of the apples in one of the buckets. However, that does not mean that having all of the apples in one of the buckets would be impossible - it would just be relatively improbable.
===Why should horses care about ensembles?===
Why does the ensemble matter in this case study? Suppose, for example, that you could not see inside of the buckets and that you were relying upon the bucket contents for a particular purpose - for example, feeding two horses from the two different buckets, which you repeated every day for a number of years. Sure, some days one horse would get slightly more food than the other, but from our knowledge that the ensemble is dominated by a 50/50 split of apples between the buckets, we can be relatively confident that both horses will be well fed.
==Ensembles and Eterna==
But enough of the horseplay - let us discuss how ensembles are important in Eterna. One key concept is that any structure you see in Eterna is only going to exist some of the time in real life. If you could somehow observe a single RNA molecule over time, it would constantly be shifting between all of the different states in the ensemble.
Even though the RNA molecule would be constantly shifting, it would be spending a higher proportion of its time in low-energy states. The natural mode structure (which is the minimum free energy structure) in Eterna is the specific state predicted to be the lowest energy, so it is the single state that we would expect to see the most. However, this does not necessarily imply that we observe this state even a majority of the time - the specific probabilities involved would depend on the relative energies of the different states.
===Importance in Eterna===
Why does the ensemble matter in Eterna? Suppose you are designing an RNA to match a target structure. A strategy that focuses on minimizing the energy of the target structure may not necessarily be the best strategy. Sometimes there is an RNA structure that we are trying to avoid. If so, it is very important to keep the entire ensemble in mind instead of just the target structure, as we want to increase the probability of the target structure while keeping the probability of the undesired structure low.
==See also==
