How do you keep waters and ions out of a ligand binding pocket during MD simulation

Hi GROMACS community,

I’m looking for a way to keep waters and ions out of a ligand binding pocket during MD simulation.

The protein I’m interested in is a membrane protein, whose ligand binding pocket is filled with several random waters in the apo form.

I want to see what happens if I intentionally keep the waters (and ions) out of the pocket during the simulation, and discuss the roles of the waters in the pocket.

I hoped to be able to do something like the following, but I couldn’t find how can I set up such a simulation so far. (I’m a newbie to MD simulation.)

  • Calculate the CoG of the binding pocket.
  • Apply repulsive forces to waters and ions within certain distance from the CoG. (By something like the flat-bottomed harmonic potential.)
  • But don’t want to apply any counteracting forces on the protein side.
  • The CoG must be periodically updated, because the protein is not confined its position in the simulation box.

My question is, how would you go about doing such a simulation? Is it possible with gromacs?

I appreciate any comments from the community.

Thanks in advance

You could try to use virtual site (for CoG of the binding Methods — GROMACS 2021.5 documentation)
and define a repulsive potential between the virtual site and O of water molecules and ions.


Thank you for your suggestion. I’ll check it out.