Hi
As you know we should remove (reference) ligand from protein structure to put new ligand for docking. removing ligand or So4/po4 group has clear reason, but in commercial docking software like GOLD ,Glide and FlexX we try remain water molecule in active site,however in free soft like auto-dock all water molecule remove from protein structure.So, my question is that in protein with metal ion that have important effect in binding (as result in score or free energy) between ligand and protein, we must remove metal ion?
Best regards,
Mohamad
There is probably no hard and fast answer. If the metal is located at the binding site and coordinates to the ligands you are docking then it needs to be included, if its not directly involved in ligand binding then you might be able to remove but you should adjust the charges of residues near the metal to account for its effect. Docking onto a metal ion can be tricky, in Gold you can define a template that reflects the appropriate coordination structure and then dock to the template. This works pretty well.
Dear prof Reichert
Thanks for answer, at the past we discuss about protein structure change after docking. its unsolved issue in my mind, when we remove this compound like So4/Po4 , Water and metal ion ... it will be change the protein structures for docking or Not?
we try to simulate protein-ligand Complexing but when we do these change, probably we cant do this process like in Vivro environment, so its correct way?
best
mohammad
As David said there is no easy/correct answer to this problem.
If you want to be as accurate as possible, you should equilibrate the protein after removing the ligand it was co-crystallized with, since the conformation of the complex may be different from the proten conformation in the unbound (apo) form. This procedure is, unfortunately, lengthy, expensive and does not guarantee any success, since we usually don't have any information about the structure of the apo form.
So usually we simplify things and assume that the protein conformation does not change much (or at all) when a different ligand is bound. This assumption is valid for many cases, but in general you can't be ever sure that it's true for your system, unless you'll get the experimental proof.
Removing the metal ion is also tricky: it might work if it's far from the binding site, it's probably not gonna work if it's close to the binding site or interacting with the ligand.
It depends on the location of the metal group and its role in the catalysis. If it is known to interact with substrate/inhibitor you should include it.
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