Section 18.3.2.1. Choice of properties for restraint

Standard refinement procedures usually include the use of harmonic restraints of bond lengths, bond angles, planarity and `improper' dihedrals, which, along with nuclear repulsions, comprise the `hardest' restraints. Other geometric properties, such as dihedral angles, electrostatic interactions, Ramachandran energies etc., can contribute further information to the refinement; these softer restraints can either distort the structure if weighted too strongly, or not contribute significantly to the refinement if weighted too weakly. Further, the softer restraints may be more useful as statistical parameters for judging the quality of a structure than as refinement parameters themselves. Particular care should be taken when refining with significant electrostatic energies: the forces have significant effects over long ranges, are usually based on simplified polarizability models and usually arise from assumptions of standard intrinsic pK_a values.