Ebook: Evolving Methods for Macromolecular Crystallography: The Structural Path to the Understanding of the Mechanismof Action of CBRN Agents

This volume comprises papers presented at the 2005 edition of the “Crystallography of Molecular Biology” courses that have been held since 1976 at the Ettore Majorana Centre for Scientific Culture in Erice, Italy. This series of courses is renowned for bringing leaders in the field of macromo- cular crystallography together with highly motivated students, in a beautiful and intimate location that encourages people to interact. The warm and informal atmosphere at these Erice conferences, especially these on cryst- lography, has helped to foster long-term scientific interactions and new int- national friendships that have often lasted for the lifetime of the scientists. The course was financed by NATO as an Advanced Study Institute and by the European Commission as a EuroSummerSchool. The papers span the breadth of material presented in the course, which emphasized the practical aspects of modern macromolecular crystallography and its applications. One must start with crystals: Bergfors showed how to improve initial crystals through seeding, while Byrne discussed the difficult problem of crystallizing membrane proteins. The collection of optimal diffraction data requires both careful preparation of cryo-cooled crystals (Garman) and proper processing of the diffraction images (Leslie). To obtain images of electron density, one needs estimates of the phases of the diffracted spots. Sheldrick presented the background to the sing- wavelength anomalous diffraction (SAD) method, which has been gaining popularity, and McCoy discussed the basis of modern maximum likelihood methods for treating information in experimental phasing.

X-ray crystallography is the pre-eminent technique for visualizing the structures of macromolecules at atomic resolution. These structures are central to understanding the detailed mechanisms of biological processes and to discovering novel therapeutics using a structure-based approach. Currently, structures are known for only a small fraction of the proteins encoded by human and pathogenic genomes. To counter the myriad modern threats of disease, there is an urgent need to determine the structures of the thousands of proteins whose structure and function remain unknown.

This volume draws on the expertise of leaders in the field of macromolecular crystallography to illuminate the dramatic developments that are accelerating progress in structural biology. Their contributions span the range of techniques from crystallization through data collection, structure solution and analysis. The book shows how modern high-throughput methods are contributing to a deeper understanding of medical problems.