High-throughput Technologies for Structural Biology: The Protein Structure Initiative Perspective

Macromolecular X-ray crystallography has seen remarkable progress in recent years, contributing significantly to the success of structural genomics and cutting-edge structural biology efforts. These advances were made possible by the development of third-generation synchrotron sources and brought a new dimension to X-ray protein crystallography. It allowed for efficient structure phasing approaches with anomalous signal, the use of very small crystals and studies of very large macromolecular assemblies. Similar progress has been made in the field of NMR that continues to be an important contributor in structural biology. NMR is being applied to large scale projects and new technological advances allow one to address challenging proteins. These advances could not have been exploited fully, were it not for complementary progress in bioinformatics, molecular biology, proteomics, hardware and software for crystallographic data collection, structure determination and refinement, databases, robotics and automation of many processes. Many of these developments were driven by the US-based Protein Structure Initiative and other worldwide structural genomics and proteomics efforts. These developments provide a robust foundation for structural genomics and structural biology programs and assure a productive future. In this chapter, we focus mainly on reviewing X-ray crystallography technologies and their application to large- and small-scale structural genomics and structural biology programs.