Distance geometry analysis of the benzodiazepine binding site.

The in vitro binding constants to brain benzodiazepine receptor are known for a variety of benzodiazepines and also for four other different classes of strongly binding compounds. The binding data for a total of 29 drugs selected from these 5 classes was used to deduce a possible binding site model consisting of 15 site points and only 5 adjustable energy parameters. Even though some of the chemical structures differed radically, it was possible to fit the experimental data with a root mean square deviation of 1.1 kcal/mole. Apparently 5 non-hydrogen atoms in each ligand can occupy corresponding points in the site, and thus constitute a possible benzodiazepine pharmacophore.