Small-molecule crystal structures as a structural basis for drug design.

For a long time, the crystal structures of small molecules were regarded as useful only for establishing the stereochemical formulae of the crystallized compounds. Recently, chemists have realized that in the study of the environment in the solid state there exists valuable structural information on the binding characteristics of chemical groups. Numerous comparisons have been made which show the nearly perfect correlation between small-molecule structural results, and the observed binding in receptor-substrate complexes. Moreover, the observed conformations of flexible substrates interacting with the neighbouring molecules in their crystal structures, can lead to valuable hypotheses on their conformation when bound in the active site of a biological macromolecule.