Fully automatic macromolecular crystallography: the impact of MASSIF-1 on the optimum acquisition and quality of data

Automation is beginning to transform the way data are collected in almost all scientific disciplines. The combination of robotics and software now allows data to be collected consistently and reproducibly, eliminating human error and boredom. This approach has been applied to macromolecular crystallography at MASSIF-1, a fully automated beamline at the European Synchrotron Radiation Facility (ESRF). Considerable human effort is still dedicated to evaluating protein crystals in order to find the few crystals that diffract well or collecting hundreds of data sets to screen potential new drug candidates. The combination of ESRF-developed robotic sample handling and advanced software protocols now provides a new tool to structural biologists. Not only is the beamline used efficiently, running 24 h a day without getting tired, data collection is also performed consistently by an expert system, often better than with a human operator. In this review, we will focus on the impact this level of automation has had on the optimum acquisition of data from crystals of biological macromolecules.

[1]  Adam Round,et al.  ISPyB for BioSAXS, the gateway to user autonomy in solution scattering experiments , 2015, Acta crystallographica. Section D, Biological crystallography.

[2]  R. Ravelli,et al.  The use of a mini-κ goniometer head in macromolecular crystallography diffraction experiments , 2013, Acta crystallographica. Section D, Biological crystallography.

[3]  Graeme Winter,et al.  xia2: an expert system for macromolecular crystallography data reduction , 2010 .

[4]  Kurt Wüthrich,et al.  Structural Biology and Crystallization Communications the Jcsg High-throughput Structural Biology Pipeline , 2022 .

[5]  T. Schneider Synchrotron radiation: Micrometer‐sized x‐ray beams as fine tools for macromolecular crystallography , 2008, HFSP journal.

[6]  D. F. Koenig,et al.  Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Angstrom resolution. , 1965, Nature.

[7]  M. Bowler,et al.  Direct cryocooling of naked crystals: are cryoprotection agents always necessary? , 2011, Acta crystallographica. Section D, Biological crystallography.

[8]  B. L. Sibanda,et al.  Crystal Structure of DNA-PKcs Reveals a Large Open-Ring Cradle Comprised of HEAT Repeats , 2009, Nature.

[9]  Anatoly Snigirev,et al.  X-ray transfocators: focusing devices based on compound refractive lenses , 2010, Journal of synchrotron radiation.

[10]  A. Samel,et al.  Accidents and Sleepiness: A Consensus Statement from the International Conference on Work ours, Sleepiness and Accidents, Stockholm, September 8-10, 1994 , 1994 .

[11]  Adam Round,et al.  The status of the macromolecular crystallography beamlines at the European Synchrotron Radiation Facility , 2015 .

[12]  Chenghua Shao,et al.  Trendspotting in the Protein Data Bank , 2013, FEBS letters.

[13]  Olof Svensson,et al.  Experimental procedure for the characterization of radiation damage in macromolecular crystals , 2011, Journal of synchrotron radiation.

[14]  Olof Svensson,et al.  Automatic processing of macromolecular crystallography X-ray diffraction data at the ESRF , 2013, Journal of applied crystallography.

[15]  A Beteva,et al.  High-throughput sample handling and data collection at synchrotrons: embedding the ESRF into the high-throughput gene-to-structure pipeline. , 2006, Acta crystallographica. Section D, Biological crystallography.

[16]  F Cipriani,et al.  Automation of sample mounting for macromolecular crystallography. , 2006, Acta crystallographica. Section D, Biological crystallography.

[17]  Didier Nurizzo,et al.  The Upgrade Programme for the Structural Biology beamlines at the European Synchrotron Radiation Facility – High throughput sample evaluation and automation , 2013 .

[18]  Nathan Nelson,et al.  Crystal structure of plant photosystem I , 2003, Nature.

[19]  Krista Joosten,et al.  PDB_REDO: constructive validation, more than just looking for errors , 2012, Acta crystallographica. Section D, Biological crystallography.

[20]  Takashi Kumasaka,et al.  Mail-in data collection at SPring-8 protein crystallography beamlines , 2008 .

[21]  DeMarco V Camper,et al.  Fully automated protein purification. , 2009, Analytical biochemistry.

[22]  S. Brockhauser,et al.  Automation and Experience of Controlled Crystal Dehydration: Results from the European Synchrotron HC1 Collaboration , 2015 .

[23]  Olof Svensson,et al.  Automation of macromolecular crystallography beamlines. , 2005, Progress in biophysics and molecular biology.

[24]  Sebastien Petitdemange,et al.  Diffraction cartography: applying microbeams to macromolecular crystallography sample evaluation and data collection. , 2010, Acta crystallographica. Section D, Biological crystallography.

[25]  B. Lengeler,et al.  A compound refractive lens for focusing high-energy X-rays , 1996, Nature.

[26]  Olof Svensson,et al.  The use of workflows in the design and implementation of complex experiments in macromolecular crystallography , 2012, Acta crystallographica. Section D, Biological crystallography.

[27]  Stephen K Burley,et al.  Rapid-access, high-throughput synchrotron crystallography for drug discovery. , 2012, Trends in pharmacological sciences.

[28]  J. Kendrew,et al.  A Three-Dimensional Model of the Myoglobin Molecule Obtained by X-Ray Analysis , 1958, Nature.

[29]  Michael Becker,et al.  Mail-in crystallography program at Brookhaven National Laboratory's National Synchrotron Light Source. , 2006, Acta crystallographica. Section D, Biological crystallography.

[30]  Randy J. Read,et al.  Overview of the CCP4 suite and current developments , 2011, Acta crystallographica. Section D, Biological crystallography.

[31]  M. Selmer,et al.  Structure of the 70S Ribosome Complexed with mRNA and tRNA , 2006, Science.

[32]  D. Dawson,et al.  Fatigue, alcohol and performance impairment , 1997, Nature.

[33]  E. Garman,et al.  Optimizing the spatial distribution of dose in X-ray macromolecular crystallography. , 2013, Journal of synchrotron radiation.

[34]  Andrzej Joachimiak,et al.  High-throughput crystallography for structural genomics. , 2009, Current opinion in structural biology.

[35]  Olof Svensson,et al.  Fully automatic characterization and data collection from crystals of biological macromolecules , 2015, Acta crystallographica. Section D, Biological crystallography.

[36]  Gebhard F. X. Schertler,et al.  Structure of a β1-adrenergic G-protein-coupled receptor , 2008, Nature.

[37]  Yan Li,et al.  Structure of the Pds5-Scc1 Complex and Implications for Cohesin Function. , 2016, Cell reports.

[38]  Aina E Cohen,et al.  An automated system to mount cryo-cooled protein crystals on a synchrotron beam line, using compact sample cassettes and a small-scale robot. , 2002, Journal of applied crystallography.

[39]  Olof Svensson,et al.  ISPyB: an information management system for synchrotron macromolecular crystallography , 2011, Bioinform..

[40]  Elspeth F Garman,et al.  Absorbed dose calculations for macromolecular crystals: improvements to RADDOSE. , 2009, Journal of synchrotron radiation.

[41]  M. Yusupov,et al.  Crystal Structure of the Eukaryotic Ribosome , 2010, Science.

[42]  A. N. Popov,et al.  Optimization of data collection taking radiation damage into account , 2010, Acta crystallographica. Section D, Biological crystallography.

[43]  M. Bowler,et al.  Measurement of the intrinsic variability within protein crystals: implications for sample-evaluation and data-collection strategies. , 2014, Acta crystallographica. Section F, Structural biology communications.

[44]  P Theveneau,et al.  ID14 'Quadriga', a Beamline for Protein Crystallography at the ESRF. , 1998, Journal of synchrotron radiation.

[45]  Didier Nurizzo,et al.  RoboDiff: combining a sample changer and goniometer for highly automated macromolecular crystallography experiments , 2016, Acta crystallographica. Section D, Structural biology.

[46]  T. Richmond,et al.  Robots, pipelines, polyproteins: Enabling multiprotein expression in prokaryotic and eukaryotic cells , 2011, Journal of Structural Biology.

[47]  Didier Nurizzo,et al.  Recent progress in robot-based systems for crystallography and their contribution to drug discovery , 2013, Expert opinion on drug discovery.

[48]  L Jacquamet,et al.  Upgrade of the CATS sample changer on FIP-BM30A at the ESRF: towards a commercialized standard. , 2009, Journal of synchrotron radiation.

[49]  Victor S Lamzin,et al.  Automated detection and centring of cryocooled protein crystals. , 2006, Acta crystallographica. Section D, Biological crystallography.

[50]  Gyorgy Snell,et al.  Automated sample mounting and alignment system for biological crystallography at a synchrotron source. , 2004, Structure.

[51]  Stéphanie Malbet-Monaco,et al.  How the ESRF helps industry and how they help the ESRF , 2013, Acta crystallographica. Section D, Biological crystallography.

[52]  Richard Henderson,et al.  CryoEM at IUCrJ: a new era , 2016, IUCrJ.

[53]  John R. Helliwell,et al.  Experiences with archived raw diffraction images data: capturing cisplatin after chemical conversion of carboplatin in high salt conditions for a protein crystal , 2013, Journal of synchrotron radiation.

[54]  D. F. Koenig,et al.  Structure of Hen Egg-White Lysozyme: A Three-dimensional Fourier Synthesis at 2 Å Resolution , 1965, Nature.

[55]  Bertram Ludaescher,et al.  AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery. , 2013, Acta crystallographica. Section D, Biological crystallography.

[56]  Didier Nurizzo,et al.  MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments , 2010, Journal of synchrotron radiation.

[57]  Olof Svensson,et al.  EDNA: a framework for plugin-based applications applied to X-ray experiment online data analysis. , 2009, Journal of synchrotron radiation.

[58]  John R. Helliwell,et al.  Experience with exchange and archiving of raw data: comparison of data from two diffractometers and four software packages on a series of lysozyme crystals , 2012, Journal of applied crystallography.

[59]  A. N. Popov,et al.  MeshAndCollect: an automated multi-crystal data-collection workflow for synchrotron macromolecular crystallography beamlines , 2015, Acta crystallographica. Section D, Biological crystallography.

[60]  G. Waldo,et al.  Library methods for structural biology of challenging proteins and their complexes. , 2013, Current opinion in structural biology.

[61]  Konrad Büssow,et al.  Facilities and methods for the high-throughput crystal structural analysis of human proteins. , 2003, Accounts of chemical research.

[62]  W. Kühlbrandt The Resolution Revolution , 2014, Science.

[63]  Armin Wagner,et al.  Protein crystallography with a novel large-area pixel detector , 2006 .

[64]  D Spruce,et al.  Automation of the collection and processing of X-ray diffraction data -- a generic approach. , 2002, Acta crystallographica. Section D, Biological crystallography.

[65]  Elspeth F Garman,et al.  Experimental determination of the radiation dose limit for cryocooled protein crystals. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Satyavati Kharde,et al.  The structure of Rpf2–Rrs1 explains its role in ribosome biogenesis , 2015, Nucleic acids research.

[67]  Bernhard Rupp,et al.  Approaches to automated protein crystal harvesting. , 2014, Acta crystallographica. Section F, Structural biology communications.

[68]  Anastassis Perrakis,et al.  Automated protein model building combined with iterative structure refinement , 1999, Nature Structural Biology.

[69]  Florent Cipriani,et al.  CrystalDirect: a new method for automated crystal harvesting based on laser-induced photoablation of thin films. , 2012, Acta crystallographica. Section D, Biological crystallography.

[70]  Tom Alber,et al.  Automated protein crystal structure determination using ELVES. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Nicholas K. Sauter,et al.  Automated diffraction image analysis and spot searching for high-throughput crystal screening , 2006 .