Rational design
The range of technologies now available for rational drug design is huge. For example, once a drug target has been identified its properties can be characterised by computer ('in silico') and this information used to inform drug design. Crystallographic techniques and computer-aided prediction can be used to construct the structure of the binding site in three dimensions (Fig 5). The ability of drug molecules to interact with the receptor can then be modelled before any drug product is synthesised.
These techniques are very powerful when combined with the huge chemical libraries held by pharmaceutical companies. The rate-limiting factor has shifted from the creation of the drug molecule to the identification of suitable targets and the characterisation of their role in the pathophysiology of the condition of interest.
Fig 5 A computer model of a receptor molecule that allows the structure/activity relationships of potential candidate ligands to be predicted in silico before any molecule is synthesised or tested in vitro.
