Docking drugs in membrane protein cavity

HADDOCK
1

Dear Prof Bonvin and All,

I am interested to dock some drugs in the cavity of a membrane protein; process and analysis proceed correctly, even if in some cases the drugs is docked outside the binding-site of the cavity (just under the selectivity filter). I suppose the issue is in the selection of active/passive residues, so I would gently to know if there is a way to select a box with center and size coordinates, such as in Autodock.
I can share all files if needed. Thanks in advance.

Francesco

2

Hi Francesco

I am interested to dock some drugs in the cavity of a membrane protein; process and analysis proceed correctly, even if in some cases the drugs is docked outside the binding-site of the cavity (just under the selectivity filter). I suppose the issue is in the selection of active/passive residues, so I would gently to know if there is a way to select a box with center and size coordinates, such as in Autodock.

You can’t define a box like in autodock.

Two options:

  1. Define active residues lining up the box

  2. Define a shape into the binding site and define restraints to that shape. Check for that the following tutorial:

https://www.bonvinlab.org/education/HADDOCK24/shape-small-molecule/

Also, if your binding site is rather buried, decreasing the intermolecular interactions might help getting the ligand into it (step 10 in the above tutorial).

Cheers
Alexandre