Integrating Structural and Functional Genomics

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Structural genomics has provided many three-dimensional structures of proteins with unknown or poorly defined function where analysis of the fold suggests a possible binding site for small molecules. An approximate function may be evident from the structure but, most often, the specific target ligand remains unknown. This is a widespread observation in structural genomics programs and demonstrates the limits of structure-based approaches to determining function. Methods to identify the natural target ligands for such proteins, and therefore bridge structural and functional genomics studies, are discussed.