Section 18.3.2.8. Special geometries: cofactors, ligands, metals etc.

Most crystallographers will experience neither the need nor desire to derive their own parameterization for general protein structure refinement; many, however, need new parameters for ligands or other entities that are not amino-acid residues. The accuracy required for their application will determine the appropriate effort. If the purpose of the structure is to determine the general orientation of an inhibitor for molecular modelling studies with a still lower effective accuracy, it may be that no refinement (and no parameterization) is necessary at all. As the accuracy requirements increase, so does the need for good parameterization and a way of estimating when the density is incompatible with known structures. Such incompatibility may be decisive in identifying the stereochemistry of ligands selected from racemic mixtures, or the occurrence of a chemical reaction, or even falsely characterized substances. For such applications, small-molecule structural databases will remain the only choice for parameter derivation, which can be done exactly as for amino-acid fragments.