Structure-Based Molecular Design

ses, development of intricate models for molecular recognition, and the design of novel enzyme inhibitors and therapeutical agents. Finding new drugs, in particular, is an important part of the new initiatives in health care. We will focus on discovery or design of molecules that interact with biochemical targets whose three-dimensional structures are known, a field called “structure-based” design. The idea that molecules can interact in a highly specific manner has a long history in medicinal chemistry and was well articulated by Fischer1 and Ehrlich2 a century ago using a “lock-andkey” analogy. We explore the usefulness of this concept by reviewing both general principles of molecular recognition and specific computer programs that pack molecules together. The drug discovery process is complex, typically taking 10 years for new products to reach the market. The first step is finding interesting leads. Such compounds are identified through a wide variety of routes.3 Structure-based design, spurred by the rapid