Structural genomics: beyond the Human Genome Project

With access to whole genome sequences for various organisms and imminent co mpletion of the Human Genome Project, the entire process of discovery in mo lecular and cellular biology is poised to change. Massively parallel measur ement strategies promise to revolutionize how we study and ultimately under stand the complex biochemical circuitry responsible for controlling normal development, physiologic homeostasis and disease processes. This informatio n explosion is also providing the foundation for an important new initiativ e in structural biology. We are about to embark on a program of high-throug hput X-ray crystallography aimed at developing a comprehensive mechanistic understanding of normal and abnormal human and microbial physiology at the molecular level. We present the rationale for creation of a structural geno mics initiative, recount the efforts of ongoing structural genomics pilot s tudies, and detail the lofty goals, technical challenges and pitfalls facin g structural biologists.