COnew gabbia (Page 22)

BRIEF RETROSPECTIVE OF COMPUTER-AIDED DRUG DESIGN (CADD) It has been nearly 40 years that quantitative structure-activity relationships (QSAR) methods entered into the practice of pharmaceutical and agrochemical research, opening the way to several generations of computerized rational drug design approaches. The first application of QSAR is attributed to Hansch around 1969, and its appeal may be attributed to the strength of its initial postulate that biological activity is a function the structure described by electronic attributes, hydrophobicity and steric parameters. However for many years, the approach suffered of the criticism of not being predictive, although the biological data of the known molecules (and used for the construction of the mathematical models) could be well reproduced. CADD is valuable only if it allows to predict – and not only to understand biological activities. Over the last 20 years and further to the advent of new technologies such as computer graphics, X-ray protein crystallography, theoretical chemistry and molecular modeling, extensive ligand-receptor interactions analyses became possible and many of the drawbacks of the first generation disappeared. Computer-aided rational drug design emerged as a new approach providing insights, generating increased knowledge and creativity of invaluable price. The explosion in the number of scientific articles based on computer-assisted drug design as well as the intensive filing of patents with molecular modelers, medicinal chemists and X-ray crystallographers as co-inventors, prove that CADD is now an important tool in drug discovery and development. It has become a well-established research field during the last decade due to advances in computer hardware that have brought high-performance computing and graphics within the reach of most academic and industrial laboratories.