Intervals and the deduction of drug binding site models

In the search for new drugs, it often occurs that the binding affinities of several compounds to a common receptor macromolecule are known experimentally. But the structure of the receptor is not known. We describe an extraordinarily objective computer algorithm for deducing the important geometric and energetic features of the common binding site, starting only from the chemical structures of the ligands and their observed binding. The user does not have to propose a pharmacophore, guess the bioactive conformations of the ligands, or suggest ways to superimpose the active compounds. The method takes into account conformational flexibility of the ligands, stereospecific binding, diverse or unrelated chemical structures, inaccurate or qualitative binding data, and the possibility that chemically similar ligands may or may not bind to the receptor in similar orientations