Three‐dimensional computer modeling as an aid to drug design

Three‐dimensional computer graphic systems are an emerging tool in the design of therapeutic compounds. The molecular recognition process involved in drug‐receptor interaction implies a three‐dimensional stereospecificity shared by a set of drugs of similar pharmacological action. In investigating the pharmacophore, it is therefore necessary to go beyond two‐dimensional structures by including the description of the spatial properties of drugs. This review describes both current and potential tools that a graphic computer can support to help the medicinal chemist in his structure‐activity puzzle. An outline of the systems presently in use for this purpose and a summary of recent applications is given. Some current developments undertaken in our research group are presented in the field of opiates, GABA, clonidine, antipsychotics, and S‐adenosyl‐L‐methionine inhibitors.