REVIEW Automated technologies and novel techniques to accelerate protein crystallography for structural genomics Babu A. Manjasetty 1, 2 , Andrew P. Turnbull 3 , Santosh Panjikar 4 , Konrad Büssow 5 and Mark R. Chance 1, 2 * 1 Case Center for Synchrotron Biosciences, National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY, USA 2 Case Center for Proteomics and Mass Spectrometry, Case Western Reserve University, Cleveland, OH, USA 3 Cancer Research Technology, Birkbeck College, University of London, London, UK 4 EMBL Hamburg c/o DESY, Hamburg, Germany 5 Protein Structure Factory, Helmholtz Center for Infection Research, Division of Structural Biology, Braunschweig, Germany The sequence infrastructure that has arisen through large-scale genomic projects dedicated to protein analysis, has provided a wealth of information and brought together scientists and insti- tutions from all over the world. As a consequence, the development of novel technologies and methodologies in proteomics research is helping to unravel the biochemical and physiological mechanisms of complex multivariate diseases at both a functional and molecular level. In the late sixties, when X-ray crystallography had just been established, the idea of determining protein structure on an almost universal basis was akin to an impossible dream or a miracle. Yet only forty years after, automated protein structure determination platforms have been established. The widespread use of robotics in protein crystallography has had a huge impact at every stage of the pipeline from protein cloning, over-expression, purification, crystallization, data collection, structure solution, refinement, validation and data management- all of which have become more or less automated with minimal human intervention necessary. Here, recent advances in protein crystal structure analysis in the context of structural genomics will be discussed. In addition, this review aims to give an overview of recent developments in high throughput instrumentation, and technologies and strategies to accelerate protein structure/function analysis. Received: July 12, 2007 Revised: October 16, 2007 Accepted: October 17, 2007 Keywords: Protein structure analysis / Structural genomics / Structural proteomics / X-ray crystallography Proteomics 2008, 8, 0000–0000 1 1 Introduction Proteins are fundamental components of living cells and perform a wide variety of functions. A protein is not just a sequence of amino acids or a three-dimensional structure, but a nano-machine capable of performing specialized biological functions in processes from respiration to Correspondence: Dr. Babu Manjasetty, Center for Synchrotron Biosciences, Case Center for Proteomics, National Synchrotron Light Source, Upton NY 11973, USA E-mail: babu@bnl.gov Fax: 11-631-344-5594 Abbreviations: EMBL, European molecular biology laboratory; MBP, maltose binding protein; MR, molecular replacement; PDB, protein data bank; SAD/MAD, single/multiple wavelength anom- alous diffraction; SIR/MIR, single/multiple isomorphous replace- ment; SSRL, Stanford synchrotron radiation laboratory * Additional corresponding author: Professor Mark R Chance, E-mail: mark.chance@case.edu DOI 10.1002/pmic.200700687  2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.proteomics-journal.com