Hello,

This is my first time posting a question here, and I’m hoping that someone could help me with this. I’ve been trying to dock different compounds to the active site of the Iron Superoxide dismutase protein (protein 1ids), which has an Fe atom with 3 histine and 1 aspatic acid residue bound to it. The binding pocket is very small. I’ve tried keeping all of the 4 amino acid residues bound to the Fe atom when preparing the receptor but didn’t get any clusters in the binding pocket after the sphere generation step. I think this is because the binding pocket is so small and crowded that dock can’t efficiently generate spheres inside it.

But then I tried removing the four residues bound to the Fe atom to clear up the binding site, and DOCK was able to generate a group of clusters right inside the binding pocket. I went ahead and screened a big library of ligands against the enzyme only to find out that Dock6 did not recognize the Fe atom. The docking still ran successfully but gave the warning “Fe atom type not recognized.” I pulled up the grid score results and saw that the ligands were docked in the binding pocket but they were all way too close to the Fe atom and can potentially cause clashes.

I’ve been looking for instructions on how to prepare a metalloenzyme receptor in a way that dock recognizes the metal atom and includes its interactions in the calculation but could not find one. I’m also worried that removing the ligands bound to the Fe atom will mess up my results but if I keep them, I wouldn’t be able to get the clusters right inside the binding pocket. Could somebody please enlighten me on this?

I’d appreciate and help and explanation. Thank you so much for reading through my long post!

p.s There are no known inhibitors for my protein. I’ve attached a pdb file that has the protein receptor with one of the screened compounds in its binding site. In the picture the brown sphere represents the Fe atom, and the blue spheres are the cluster.