What is the meaning of the word ensemble in terms of protein structure? Many times it's also used in combination with the concept of druggability of protein. I am unable to understand what it means when we study regarding druggability. For example the link https://www.ebi.ac.uk/chembl/drugebility/faq. Can you explain me with some basic references, if possible?
Ensemble appears to be used in a very non-standard way in the drugebility link to refer to what is usually called a consensus score, the average score generated from different prediction models in this case. From the short description (no reference available) it appears to have nothing to do with the standard definition in terms of protein structure, which is a set of possible conformations usually close to the native state which can be sampled under physiological conditions. Very odd if I am right.
If I am correct it means the following. Many proteins, especially the active/binding site is quite flexible. Therefore if you do docking with small molecule onto 1 particular conformation of the protein structure (most docking programs keep the protein fixed and the flexible docking one are not very good), it does not ultimately bind at all in experiments, as the protein is in that particular state for a very transient period of time. To tackle this, many people do what is called "ensemble docking". In this, a "ensemble" or "collection" of structures are created starting from a starting structure, using MD, structure pred. algorithms or whatever and then the docking is done on this entire ensemble of structures. Then the average score is called the ensemble score. If the ensemble score is high, with low standard deviation, the drugability of the protein is considered high.
Thank You Jeffrey and Srayanth. Its clear for me now. But I do have another query. I regularly use AutoDock 4.2 for small molecule docking. What is your opinion regarding this.
Well, if you are concerned about whether its free software or not Autodock is as good as it gets I guess.
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