ABSTRACT

I. INTRODUCTION The results of high-throughput genome sequencing are changing our thinking about biology and disease. Using databases and associated software packages, we can compare organisms at the level of whole genomes, providing important evolutionary insights and identifying clinically relevant differences between humans and their pathogens. The availability of whole-genome sequences also creates enormous possibilities for the development of massively parallel tools (such as DNA microarrays) that will contribute to both fundamental research and pointof-care diagnostics. The gene sequences themselves also offer the promise of new therapeutic agents, many of which will be protein pharmaceuticals. The revolution in genome sequencing is stimulating a corresponding reorganization of protein studies with an eye toward increasing sensitivity and throughput of methods for analyzing the abundance of proteins in cells and tissues as well as

for speeding up methods for biophysical analysis of proteins. Structural genomics has as its formative idea the concept of making structural information available for translated sequences that continue to become available. The coupling of highthroughput crystallography to use of modeling leverages the structural information derived from a single template sequence to multiple other target sequences of interest. The execution of this concept is being refined as we continue to test our ideas of structural genomics against the reality of our experience. In this chapter, we recount our progress in structural genomics, carried out under the overall umbrella of the New York Structural Genomics Research Consortium (NYSGRC), www.nysgrc.org.