e-HTPX
www.e-htpx.ac.uk
An e-science resource for high throughput
protein crystallography
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
Overview of Protein Crystallography
Crystallisation
Data Collection
Phasing
Protein Production
Protein Structure
Target
Selection
Structure analysis
Deposition
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
Key Components
Access to
• Instruments
• Databases
• Computing Facilities
• Real samples transferred
• Security
• Safety
• Automation
Tests many e-science procedures
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.
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
The Data Model
MAPPING
MMCIF
XML/SQL/mmCIF
Dictionary
Protein production
Crystallisation
Data Collection
Phasing
Refinement
UML
Code Generation
Analysis
DATA MODEL
(classes)
Deposition
Properties of data model
Must be
•readily extensible
•relatively easy to maintain
•relatively easy to understand
•able to cope with realities of projects
•mappable to established formats
A single standard defining an
agreed method for representation
and structure of the data using UML
for the primary description
Crystallisation Facilities
Web Site Session View
Click on a well …
Have I got Crystals?
Remote Submission of Crystals to Synchrotron
Database on Beamline
Sample Changer and goniometry on SRS
Automatic Data Collection with DNA
e.g. ISPyB
e-HTPX
contribution
Feedback of Results
Submitting Jobs via the Grid e.g. Service for Multiple
Model Molecular Replacement Search
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
User Issues
Users more used to hands on approach
Hurdle of obtaining Grid Certificates (but allows single sign on)
Security and reliability
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
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
e-HTPX Grant Holders
BM14 ESRF
Cambridge
Cardiff
Daresbury
EBI
Oxford
York
Martin Walsh
Randy Read
Omer Rana
Rob Allan, Greg Diakun, Martin Guest,
Colin Nave, Miroslav Papiz, Martyn Winn
Kim Henrick
Robert Esnouf, David Stuart,
Kevin Cowtan
1.4M from BBSRC + 127K from DTI
4 year Project
www.e-htpx.ac.uk
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
e-HTPX SAC
Rod Hubbard (chair)
Simon Phillips
David Brown
Peter Kuhn
Omer Rana
Randy Read
Christian Cambillau
Charlotte Capener (BBSRC Observer)
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?