ABSTRACT
The vast majority of drugs currently in use were identified by a combination of serendipity and mass screening of huge collections of compounds. While this approach has led to the development of unique therapeutic concepts and spectacular drugs, and sometimes to strong patent positions, this process of drug discovery has been a laborious one. For example, it is estimated that only 1 in 40,000 to 100,000 of the compounds initially screened as anticancer agents reach the clinic (Oldham, 1985). Thus, there is great economic benefit to be derived from improving the odds of identifying drug candidates. Rational drug design, where drugs are designed based on the knowledge of three-dimensional structures of the interacting molecules, has always been an attractive alternative and a scientifically satisfying approach; but the technological barriers which faced the structure-based approach were high in the past. This situation has undergone a dramatic change over the last decade, and structure-based drug design is at a stage closer to fruition. This change has been brought about by revolutions in two fields, biotechnology and computer technologies (Hodgson, 1990, 1991).
