This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Modern drug discovery incorporates a target-based approach, wherein a macromolecular drug target (typically a protein) is chosen. The three-dimensional structure of the target is determined, usually by x-ray crystallography, and the detailed three-dimensional coordinates of the target active site are used for in silico screening and the design of initial lead compounds. Subsequent target:lead-compound structures are used to guide the design of the next series of lead compounds. This process iterates until the lead compound has suitable properties and is of high enough quality to be a drug. Our current drug discovery efforts focus on novel targets for the treatment of cancer, bacterial diseases, and viral diseases, particularly hepatitis C virus. These research efforts require MAD/SAD data collection time in excess of the time provided to us by our PRT membership. This proposal outlines a request for additional MAD time to support our drug discovery e
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