Hello;
I want to do molecular docking with the FTO protein. PDB identity of this protein: 3LFM. While doing the docking process, I will delete the inhibitors named 3-methylthymidine and N-OXALYLGLYCINE, and prepare the pdbqt file, where I will do the hydrogen addition and the charge addition. My question is: Apart from these two chemical residues, there is also an iron atom group in the structure. Should I delete this iron atom as well?
Hello Turgut şekerler
First of all find out the binding site (pocket) for your specific protein and see that whether the metal ion is included in it or not. If it is included in the binding site than you have to include this ion for molecular docking. Second is, you can add hydrogens and charges to your proteins from Autodock tools Also you have to include your ion parameter manually as mentioned on Autodock site or else the error will be shown. I hope it works for you. You can even switch towards Pyrx as it will be more easier way to perfrom molecular docking.
All the best!
Dear @Turgut,
It is completely depends on you wheather you want the ions or not, you can keep as it is and can go for docking and it wont affect your ligand interaction. For molecular docking you need to have active site, which you already have from the point you deleted the ligand.
If you still face the problem DM to me.
This Fe(II) is a part of the catalytic site of the protein. It is a cofactor and remains bound with His231, Asp233 and His307. 3-methylthymidine and 2-oxoglutarate are the substrates, however, N-OXALYLGLYCINE instead of 2-oxoglutarate stopped the reaction. So, if you are looking for the new chealating inhibitors, you probably need this Fe(II).
Predicting coordination interactions with metals are tricky in docking. You need to optimize the partial charge on the Fe(II) first. By default, the assigned partial charge on Fe will be 0. You need to manually modify that in the .pdbqt file and test run docking with the control ligand (N-OXALYLGLYCINE) to see if the docking can reproduce the two coordination bonds with the ligand as observed in the crystal structre. In my experience, a partial charge in the range of 0.6--0.8 may be able to reproduce the coordination bond lengths in AutoDock4. Vina does not rely on partial charges and may be ineffective in this case.
Once you are able to reproduce the coordination bonds with Fe by modulating the partial charge on Fe, use that parameters to dock the new ligands.
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