198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

Supramolecular Synthons and Pattern Recognition 81
a
b
c
d
Fig. 4. Scatterplots and histograms of the spatial distribution of acceptor or donor sites in
ligand molecules about different functional groups of active site residues in ligand-protein
crystal structures (PDB) (Adapted from [65]). Note that the distributions are more smeared
when compared with those in Fig. 3
crystal structures offer a good representation of their conformations in ligandenzyme
complexes [64]. While adopting this approach, it is reassuring to note
that the average densities found for crystal structures of small organic compounds
and for the inner regions of macromolecular proteins are in the same
range. In summary, therefore, CSD derived geometries offer a considerable
simplification in the analysis and understanding of drug-receptor interaction
patterns (see also the article by J.P. Glusker in this volume).
7.3
Pharmacophore Model
The repetitive nature of enzyme-ligand patterns leads to the concept of the
pharmacophore model which postulates that there is a minimum and essential
set of functional groups that a molecule must possess in a specific geometrical
arrangement to be recognised by the receptor [66]. The pharmacophore model
can be generated by identifying the chemically important functional groups that
are common to the molecules that bind to a given receptor.
We have accordingly examined the b-lactam class of antibiotics [67]. Geometrical
details from a total of 114 b-lactams containing the fragment 56 were
retrieved from the CSD (Version 5.05) and categorised into biologically active
(80) and inactive (30) compounds. The superposition plot of 12 randomly selec-
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