I know that blind docking is most often used to determine an unknown binding site, but can it be used to determine whether a ligand is thermodynamically more likely to bind a given (known) binding site instead of another site on the target protein?
In other words, here's my thinking: if I dock a library of ligands in a given binding site, the program (VINA in my case) will give me the best poses for that particular binding site, but it won't tell me if there's a more energetically favorable site elsewhere on the protein. By doing blind docking first, I can see if the top-scoring poses for each ligand are in the given pocket or elsewhere on the protein and thus screen for ligands that are more likely to bind in a given pocket. Is this a valid rationale for starting with a blind docking even when the binding site is known?
These are just terminologies. When you define a binding site, it is no longer called a blind docking. If you are looking for a orthosteric lead molecule (a competitive inhibitor), you may define the binding site and do the screening (targeted docking). However, it is always possible for some of the orthosteric leads to have better binding affinity for a allosteric site. If you want to identify and remove those molecules form your leads library, you may run a blind docking using the leads (a smaller library). Alternatively, you may do only the blind docking and discard the poses that are not within the site of interest and consider or score only the poses that are inside the target site.
Screening the binding sites of a receptor together with screening of a ligand data base is not reasonable enough by docking simulations.
Ramin, could you explain further? Do you mean that this approach is unlikely to accurately indicate where each ligand is most likely to bind?
Using our Blind Docking approach, you can test these ideas, and you do not need to specify any concrete binding spot:
https://bio-hpc.ucam.edu/achilles/
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