Restraints schemes based on multiple distance restraints do not suffer from the inherent instabilities of Boresch restraints, and allow the ligand to be restrained to a greater extent (Figure ). In this work, harmonic or flat-bottomed distance restraints were used. Using the Figure : A ligand restrained using multiple distance restraints. Four distance restraints (r 1 -r 4 ) are applied between pairs of atoms in the ligand (blue) and the receptor (green).