Distance Geometry Receptor Mapping

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Dr. Crippen is working on the problem of understanding the specific binding of small molecules to biological receptor macromolecules. It is preferable to determine directly the structure of such complexes but the required crystallographic and/or NMR studies are much more difficult to carry out than simply measuring the binding constant. What is needed is a method of objectively deducing receptor site geometry and energetics given only the binding constants for a series of compounds. The ideal method would be completely objective and independent of assumptions by the investigator. Dr. Crippen is continuing his development of mathematical models for receptor-ligand interactions. This involves the modelling of binding energies while allowing the ligands to assume their full range of energetically allowed conformations within the site. No one else is developing methods at this level of sophistication and it is clear that the models for proteins of known structure can be tested vis- a-vis experiment thus giving confidence in the model for unknown proteins.