Efficient Drug Lead Discovery and Optimization

During the 1980s, advances in the abilities to perform computer simulations of chemical and biomolecular systems and to calculate free energy changes led to the expectation that such methodology would soon show great utility for guiding molecular design. Important potential applications included design of selective receptors, catalysts, and regulators of biological function including enzyme inhibitors. This time also saw the rise of high-throughput screening and combinatorial chemistry along with complementary computational methods for de novo design and virtual screening including docking. These technologies appeared poised to deliver diverse lead compounds for any biological target. As with many…