Interaction restraints can be applied, but this step is optional.

To restrain the docking to a particular hydrogen bond donor or acceptor in the receptor.

• Setup the Docking Project.
• Docking/Interaction Restraints.
• Select the atoms in the docking project receptor (e.g. _rec object) that you would like the ligand(s) to interact with and click on the "Add Hbond Donor/Acceptor button.

Or you can restrain by a defined moiety in the ligand with the receptor atom.

• Docking/Interaction Restraints.
• Select the atoms in the docking project receptor that you would like the ligand(s) to interact with.
• You can also define a chemical moiety that you would like to interact with the receptor. To do this click add the SMILES string or click on the button to sketch the chemical group. An attachment point needs to be defined (right click on atom and choose Attachment Point from the menu).

• A table of the restraints will be displayed. You can check the restraint on and off using the check marks in the "Active" column. You can also increase the weight.

Notes Q: How do distance constraints work in docking or modeling - are they hard filters? A: No, constraints are not hard filters. They act as harmonic force potentials: when atoms are within the defined range, no force is applied. If the distance exceeds the range, a restoring force is applied that increases with deviation. Q: How do I control the strength or tightness of a constraint? A: Use the weight parameter. A higher weight applies a stronger force when the constraint is violated, effectively making the constraint tighter. Q: With a hydrogen bond acceptor restraint, do I need to enter the minDist and maxDist values in the restraints table? A: No. The distance parameters for hydrogen bond restraints are internally preset, so you do not need to manually define minDist and maxDist in the table. Q: If I specify three active hydrogen bond acceptor restraints, will docking always find a pose that satisfies all three? A: Not necessarily. While the docking algorithm will attempt to satisfy all active restraints, success depends on whether the ligand has enough appropriately positioned hydrogen bond donors to interact with all three acceptors. If the geometry doesn't allow it, or if sampling is limited, one or more restraints may not be satisfied.