Hello everyone,
I am trying to do molecular docking using AutoDock Software. One of the struggling I am trying to deal with is generating Grid Box. How can I generate Grid Box without knowing active binding sites of the protein? Should I keep the Grid Box positions as default, or should I change it according to the binding site? Sorry for the inconvenience.
Thanks in advance,
Mervenur
Mervenur, if you don't know the specific binding site of a protein I would suggest you perform blind docking, which would involve either: a) creating multiple smaller grid boxes eventually covering the entire protein, or b) fitting the entire surface of your protein into one large grid box. These methods, however, are much less accurate than site-specific docking, so I would suggest reviewing the literature and looking for previuously reported binding sites for that specific protein, also maybe perform multiple blind dockings while contracting your grid box after finding favorable protein-ligand complex poses.
Best of luck!
Hi Mervenur,
The grid box position defines the region of the protein where the docking will be performed. Any region outside the box won't be explored during docking.
Docking is not an easy task when you don't know the binding site location, but there are several approaches you could try.
I would first look for mutagenesis data in the literature to see if there are mutations that disrupt the binding of known ligands or SAR data. That could give you some clues about the binding site location.
One other option could be to use binding site prediction tools to identify relevant pockets and perform multiple docking screens centered on each pocket.
You can also start by using a large box enclosing part of the protein and see if you can find a pocket that fits most of your ligands. However this will require higher sampling to be able to explore the whole box.
Good luck with you docking
Hi Mervenur,
As the colleagues said before, it is complicated to perform docking without knowing the active site. In this case, you would perform a blind docking, and you would get lots of different results. You can have specific active-site binding, maybe allosteric binding (depending on your protein, of course) and even unspecific binding. It takes some time and parsimony to analyze such results (although I'd say that wherever most of your results are concentrated, that is probably your active site, but it is hard to get the correct pose of the ligand in the same experiment). I would search the literature for the active site, I would search for PDBSum to check for clefts or tunnels, and then set my grid box in that area.
Best of luck,
Lorenzo
I strongly agree with all. Grid box generation teddius job in case binding site not known and if mutagenesis another threat. Find binding site then select binding site tthen set griiddbox easily..
Thank you for all your help @Vice Tomičić, @Nicolas Panel, @Lorenzo Briganti, and @Gautam Bhardwaj. All your answers really helped a lot. But I have another question. What do I need to do when I got an error saying 'couldn't find macromolecule.Cl.map' When I run autogrid it's all fine, but whenever it comes to the docking I always get this error and couldn't found any solution. What do you suggest?
Thank you,
Mervenur
Please check protein preparation. Some problem or missing in protein.
Dear Mervenur,
I suggest taking a look at the answers to these questions as they may help you to determine if you've taken all the necessary and correct steps:
1) https://www.researchgate.net/post/Autodock4_doesnt_find_the_Clmap_file_using_indomethacin_as_ligand
2) https://www.researchgate.net/post/How_to_avoid_this_Autodock_Error
Best of luck!
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