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Is there a procedure that allows me to systematically place crystal water around a particular residue, for the purpose of docking studies with Glide?

We usually recommend deleting waters from the receptor structure, because Glide has its own methods for considering the solvation environment of the ligand and active site. Also, if you will be docking multiple ligands (e.g., for screening), while an explicit water could help with docking some ligands, it could interfere with the docking of other ligands. Remember that as part of the fixed receptor structure, the water won't be able to move to accommodate different ligands.

For some situations, though, it might be helpful to include a structural water or two, especially if you will be docking a single ligand, or several ligands with very similar binding modes.

Generally, these structural waters are in the PDB crystal structure. If there are other crystal structures for this receptor, you could use water positions from those structures. There is a script on our website (Resources & Downloads → Script Center) for identifying conserved waters across multiple structures (cluster_waters.py, in the General Tools section).

If you have no information about the water locations, you could manually add waters, guided by the literature. Alternatively, you could use Impact → Soak to add explicit water to your system, and then run a Dynamics job to find potential water sites, or use Desmond to solvate the protein and run a dynamics job to equilibrate the water. Obviously, this approach is much more computationally intensive.

Once you have a water in roughly the right location, the Optimze step of the Protein Preparation Wizard will reorient the hydrogens to maximize the H-bond network (you might want to use "Exhaustive sampling", though. However, even with the Minimize step, the oxygen position won't change very much.)

If you want to examine the effect of including or excluding specific waters, you can prepare multiple grids with and without the waters and dock ligands to all of these grids with the Virtual Screening Workflow.

Keywords: waters, receptor structure, solvation, explicit water, water locations, optimize, cluster_waters.py, Glide, VSW

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