Automation of Protein Crystallography Facilities on the SRS

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e-HTPX
www.e-htpx.ac.uk
An e-science resource for high throughput protein
crystallography
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Need for High Throughput Protein Crystallography
Biochemistry provides the only experimental basis
for causal understanding of biological mechanisms
(Sydney Brenner)
Nobel Prize 2002
Protein Structures can be interpreted in
(bio)chemical terms
Experiments then carried out to test hypotheses
about the biochemical (and cellular) function of
the protein
Complex systems with large number of proteins -
high throughput required for complete description
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Overview of Protein Crystallography
Crystallisation
Phasing
Data Collection
Protein Production
Protein Structure
Target Selection
Structure analysis
Deposition
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Top Level Aim of e-HTPX
Link the various stages in to one single all
encompassing interface from which users can
initiate, plan, direct and document their
experiment either locally or remotely from a
desktop computer.
Deliver this ready for Diamond
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Key Components

• Access to
• Instruments
• Databases
• Computing Facilities
• Real samples transferred
• Security
• Safety
• Automation

Tests many e-science procedures
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Resistance to Automation
Luddites, when faced with the use of machines
(operated by less-skilled labour) to drive down
their wages and to produce inferior goods, turned
to wrecking the offensive machines and
terrorizing the offending owners in order to
preserve their wages, their jobs, and their
trades.
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Deposition of Data in PDB
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE
X-RAY DIFFRACTION REMARK 200 DATE OF
DATA COLLECTION NULL REMARK 200
TEMPERATURE (KELVIN) NULL
REMARK 200 PH
NULL REMARK 200 NUMBER OF
CRYSTALS USED NULL
REMARK 200
REMARK 200 SYNCHROTRON
(Y/N) Y REMARK 200
RADIATION SOURCE NULL REMARK 200
BEAMLINE NULL
REMARK 200 X-RAY GENERATOR MODEL
NULL REMARK 200 MONOCHROMATIC OR LAUE (M/L)
M REMARK 200 WAVELENGTH OR
RANGE (A) NULL REMARK 200 MONOCHROMATOR
NULL REMARK 200
OPTICS NULL REMARK 200

REMARK 200 DETECTOR TYPE
NULL REMARK 200 DETECTOR MANUFACTURER
NULL REMARK 200 INTENSITY-INTEGRATION SOFTWARE
NULL REMARK 200 DATA SCALING SOFTWARE
NULL REMARK 200
REMARK 200 NUMBER OF UNIQUE
REFLECTIONS NULL REMARK 200 RESOLUTION RANGE
HIGH (A) NULL REMARK 200 RESOLUTION RANGE
LOW (A) NULL REMARK 200 REJECTION
CRITERIA (SIGMA(I)) NULL REMARK 200
REMARK
200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE ()
NULL
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The Data Model
A single standard defining an agreed method for
representation and structure of the data using
UML for the primary description
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Crystallisation Facilities
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Web Site Session View
Click on a well
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Have I got Crystals?
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Remote Submission of Crystals to Synchrotron
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Database on Beamline
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Sample Changer and goniometry on SRS
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Automatic Data Collection with DNA
e.g. ISPyB
e-HTPX contribution
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Feedback of Results
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Submitting Jobs via the Grid e.g. Service for
Multiple Model Molecular Replacement Search
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Grid Portal accessing facilities at the EBI,
OPPF, YSBL, SRS or ESRF)
The Grid portal also allows users to securely
store, upload, download and move large volumes of
data between Grid-hosts Non e-HTPX arrows in green
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User Issues

• Users more used to hands on approach
• Hurdle of obtaining Grid Certificates (but allows
  single sign on)
• Security and reliability

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Developer Issues

• Transfer from Globus Toolkit 2 to Globus Toolkit
  4
• Use or otherwise of workflow tools for parts of
  the process
• Support of e-HTPX after grant ends
• Scientists required to test procedures and give
  feedback

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Achievements so Far

• Comprehensive Data Model Developed
• Specific Services Developed
• Crystallisation
• Automation of X-ray Data Collection
• Structure Solution by Molecular Replacement
• Portals to access Services
• Internal User testing in progress
• Useful feedback being obtained

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e-HTPX Grant Holders
BM14 ESRF Martin Walsh Cambridge Randy
Read Cardiff Omer Rana Daresbury Rob
Allan, Greg Diakun, Martin Guest, Colin Nave,
Miroslav Papiz, Martyn Winn EBI Kim
Henrick Oxford Robert Esnouf, David Stuart,
York Kevin Cowtan
1.4M from BBSRC 127K from DTI 4 year
Project www.e-htpx.ac.uk
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e-HTPX developers
Research Associates employed (plus others)
Ronan Keegan, David Meredith, Graeme Winter,
Michael Gleaves, CLRC Daresbury Laboratory Chris
Mayo, (Jonathan Diprose), The Wellcome Trust
Centre for Human Genetics Oxford Ludovic Launer
MRC France, c/o ESRF, Grenoble Joel Fillon, Oleg
Dolmanov (Anne Pajon, John Ionides) European
Bioinformatics Institute, Cambridge Paul Young,
York Structural Biology Laboratory
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e-HTPX SAC
Rod Hubbard (chair) Simon Phillips David
Brown Peter Kuhn Omer Rana Randy Read Christian
Cambillau Charlotte Capener (BBSRC Observer)
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Adoption of e-Science

• "the workshop of the weaver was a rural cottage,
  from which when he tired of sedentary labour he
  could sally forth in to his little garden, and
  with the spade or the hoe tend to it's culinary
  productions.
• The Industrial Revolution moved people from their
  homes to factories

Will e-Science reverse the trend?