The application of X-ray crystallography and molecular modeling can provide valuable insight into the optimization of the molecular interactions of a drug-protein complex to achieve potency and selectivity of a drug candidate. For the successful application of SBDD in a drug development program, the impact of these structural modifications required to improve potency and selectivity must be considered in the context of balancing of a multitude of drug properties and other considerations that include solubility, bioavailability, metabolism, distribution, toxicology, chemical stability, and intellectual property space. The utility of structure-based design from the medicinal chemist's perspective is described in this chapter.
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