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I have some problems with water and metals in binding site when using Autodock Vina.

Is it possible to make these flexible? They unfortunately remain where they are what leads to wrong interactions.

My other idea would be to delete it before docking, reinsert them and minimize everything.

Does anyone have a solution for metalloenzymes? (e.g. PDB:3NJY)

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For the water molecules, you can try hydrated ligand docking in which they are added in the ligand file. The documentation here: http://autodock.scripps.edu/resources/autodock-hydrated-docking. I am not sure if the same approach can be used for the metal atom.

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Based on my experience with Autodock Vina, it is primarily limited to non-metallic proteins in terms of reliability. This limitation is especially relevant for proteins where metals play functional roles, such as the metallic centers in oxidoreductases. A different story goes if you are willing to do QM calculations to derive modified partial charges and set up your own model systems in a more reliable way. The core issue is that significant covalent bonding involving the metal must be considered when analyzing interactions with the binding site or ligand and this affects partial charges and thus docking scores.

Therefore, I recommend switching to software better suited for accurately modeling metalloenzymes:

  1. Wang K. GPDOCK: highly accurate docking strategy for metalloproteins based on geometric probability. Brief Bioinform. 2023 Jan 19;24(1):bbac620. doi: 10.1093/bib/bbac620. PMID: 36642411.
  2. Bai F, Liao S, Gu J, Jiang H, Wang X, Li H. An accurate metalloprotein-specific scoring function and molecular docking program devised by a dynamic sampling and iteration optimization strategy. J Chem Inf Model. 2015 Apr 27;55(4):833-47. doi: 10.1021/ci500647f. Epub 2015 Mar 17. PMID: 25746437.

Please note that these are just two of the most recent methods. You should choose the method that best fits your needs for both accuracy and time efficiency.

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