Some common questions about using restraints in ligand docking.

[Andrew Orry]

Some Common Questions About Using Restraints in Ligand Docking

You can define hydrogen bond donor or acceptor restraints—and specify ligand group interactions—by using Docking → Set Restraints before running the docking. This helps guide the docking toward poses that satisfy key interactions of interest.

Q: How do distance constraints work in docking or modeling? Are they hard filters?
A: No, distance constraints are not hard filters. They function as harmonic force potentials: when the atoms are within the defined range, no force is applied. If the atoms move beyond that range, a restoring force is applied that grows with the deviation.

Q: How can I control how strong or tight a constraint is?
A: Use the weight parameter. A higher weight increases the strength of the restoring force when the constraint is violated, effectively tightening the constraint.

Q: For a hydrogen bond acceptor restraint, do I need to manually enter minDist and maxDist values in the restraints table?
A: No. The hydrogen bond distance parameters are preset internally, so there's no need to define minDist or maxDist yourself.

Q: If I specify three active hydrogen bond acceptor restraints, will the docking always find a pose that satisfies all of them?
A: Not necessarily. The docking algorithm will try to satisfy all active restraints, but success depends on the ligand’s geometry and sampling. If the ligand lacks suitable hydrogen bond donors or can't adopt a conformation to satisfy all three, some restraints may not be fulfilled.