Structure-based Drug Design

Almost all drugs interact with proteins, which are huge molecules with many different functions. Examples of some classes of protein are enzymes, which catalyse biochemical reactions, receptors, which interact with hormones and neurotransmitters, and transporters, which carry molecules through biological membranes.

Since proteins are involved in most of the biological processes that sustain life, they will clearly be natural drug targets. So when something goes wrong – the onset of disease – proteins are also in play. That is why it is possible to treat the symptoms of disease and in some cases cure the patient completely by using drugs that change protein activity. That may sound simple, but in practice it is a major challenge.

A good starting point in the production of new drugs is to elucidate the three-dimensional structure of the target molecule. A good analogy is to think of the drug as a key and the target molecule as a keyhole. The key’s role is to open or close the functionality of the protein.

In order to find the key that fits exactly, it is important to know the shape of the keyhole. Medicinal chemists can use this knowledge to design drugs (keys) that fit perfectly into the keyhole and open the lock. Or they can design drugs (keys) that fit into the keyhole in a way that prevents the lock from closing. In either case, the process is called structure-based drug research.