Chapter 9 Making New Antibiotics 145 By examining how the X-rays bounce off the target relative to known reference points, the position of every atom in the test molecule can be deduced. When the structure of a protein is known, it is often possible to identify parts of the protein crucial for its activity. The structure can then be entered into a computer program along with structures of potential inhibitors. The computer program then attempts to fit (dock) the "inhibitor" with binding sites on the target protein. This in silico or computational strategy to drug design enables chemists to examine millions of compounds for protein binding before beginning laboratory-based work. Compounds calculated to be best at binding the protein active site are then synthesized, examined for inhibition of the protein's function, and tested for activity against cultured pathogens. When active compounds are found, docking these compounds onto the protein structure provides a picture of drug-protein binding that can be used to rationally design next-generation compounds. This type of strategy led to inhibitors of HIV protease. As with high-throughput screening, structure- and computer-assisted drug design depends on first establishing a suitable target protein. Such proteins are often termed "druggable," which indicates that inhibiting the protein by a small molecule is a likely therapeutic option.