[Modeling of protein-ligand interaction complexes as a basic of the rational design of drugs]

Most of our today"s drugs have been discovered by the lucky coincidences called serendipity. The drugs itself however, have tremendously changed since the ancient times. From the herbal teas as the remedies of our ancestors, we have switched to modern therapeutics, mostly containing only one, very high active compound. Modern analytical methods and the approaches of recent molecular biology have revealed the molecular mechanisms of a lot of this high active drugs. In most of the cases, interaction of the drug molecule with a special protein in the body, located on the surface of the cell releases the biological response. This may lead to the idea, that knowledge of the structure of the protein-ligand complex enables us to design a drug with certain properties on the computer screen. If successful, serendipity could be considerably reduced as well as animal testing. As a matter of fact, it can be shown, that the combination of biophysics, modeling, and biological in vitro methods brings us very close to that goal. However, basic problems, for instance in the handling of complex systems are opposed to the reductionistic approach in the drug research. They prevent the simple application of the lock and key principle in making a drug by fitting a putative drug molecule into the binding site of a receptor. Nevertheless, whenever a biologically active compound has been discovered, be it by pure chance, serendipity, design or ethnological pharmacy, molecular modeling or drug design will be of great help in optimizing the active compounds and enrichment of the whole new class of therapeutics.