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What to do after protein-ligand docking? Is there any necessary or enhancement step recommended after docking to validate the confirmation of highest score is the best? For your information, I am using CCDC GOLD for docking and GOLD score as my scoring function.

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    $\begingroup$ Why do you need to to a docking? Do you have a biological question? For example, I want to know if this drug docks to this receptor. To validate the docking you usually test it in real life... $\endgroup$
    – llrs
    Apr 12 '19 at 10:52
  • $\begingroup$ If you really have to, you can try different docking algorithms and scoring FF. However, you might get subtle differences due to how your ligand is parameterised. $\endgroup$ Nov 16 '19 at 22:42
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You can run a Molecular Dynamics simulation to see if the pose is stable and whether the protein changes/adapts it’s conformation.

You can calculate the ligand efficiency, the docking score divided by the number if heavy atoms, and rank the compounds accordingly.

You can also compare the scores of known ligands to the experimental values and see if the docking the scores are predicting known ligands or correlate with the experimental ones.

At some point you have to make a selection and purchase or synthesize the compounds. How many compounds can you test experimentally? How many can you purchase? What is the purpose of these ligands going to be? Drugs? Did you screen the correct set of ligands e.g. a library of lead compounds that are ready to purchase for cheap, that would be a good start.

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  • $\begingroup$ To further this answer, a form of steered MD that I have found promising is (dynamic undocking)[nature.com/articles/nchem.2660]: your ligand gets yanked out. The output is not super clear though and requires some manual checking. $\endgroup$ Nov 16 '19 at 22:38

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