Hho1p GI and GII domain structres'

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The CcpNmr Software Suite 4th CCPN Annual
Conference Ambleside, 16 August 2004 Wayne
Boucher and Tim Stevens Cambridge University
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CcpNmr Analysis

• An efficient NMR assignment program
• Inspired by Ansig and Sparky
• Based on the CCPN NMR data model
• Cross platform
• Linux, Mac OSX, SGI, Solaris
• Scalable and extensible
• A universal platform for assignment
• Releases
• 1.0 b, September 2003
• 1.0, Autumn 2004

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NMR Data

• Experiments, spectra, peaks
• Molecular system information
• Complexes, chains, residues, disulphides
• Assignment information
• Including incomplete and ambiguous
• NMR measurements
• Chemical shift, relaxation rates, couplings
• Constraints for structure calculations
• Distance, dihedral
• Resonance is central

Experiment Spectra Conditions
Measurement Chemical Shift Relaxation Coupling
Constraint Distance Dihedral
Peak Dimensions
Resonance
Annotation Spin System Connectivity Residue Type
Structure Co-ordinates
Molecule Atoms Residues Chains
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Spectra

• N-dimensional windows
• Multiple spectra per window
• Automatic spectrum mapping
• Unlimited windows
• Contours on fly
• Peak aliasing
• Linked navigation
• Gradient colour schemes
• Right mouse button menu
• Keyboard shortcuts
• Blocked data (Azara, Felix, NmrPipe, UCSF)
• Hard copy (PostScript, PDF)

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Assignment Strategies

• Anonymous and intermediate
• Fully anonymous - project start
• Atom type only
• Residue type only
• Can assign to multiple contributions
• Ambiguous NOES
• Unresolvable chemical shifts
• Choose from short resonance list
• Ranked by shift difference, distance given a
  structure etc
• Can assign multiple peaks easily
• e.g. All of a spin system to its backbone root

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Resonances

• An assignable phenomenon
• Not atoms
• Not chemical shifts
• Multiple chemical shifts
• Different conditions
• Same origin
• Multiple and ambiguous atoms
• Equivalency e.g. methyl
• Prochirals e.g Hb2 or Hb3?

Experiment Spectra Conditions
Measurement Chemical Shift Relaxation Coupling
Constraint Distance Dihedral
Peak Dimensions
Resonance
Annotation Spin System Connectivity Residue Type
Structure Co-ordinates
Molecule Atoms Residues Chains
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Molecular Database

• Molecule information from the EBIs Macromolecular
  Structure Database group
• E-MSD relational database contains all PDB
  information
• Over 4000 reference chemical components defined
• E.g. ALA, ADP, Zn,
• Easily extendable to full range of organic
  molecules
• Recognises standard codes used in PDB files

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Chemical Shift References

• Available within CcpNmr software
• Graphs and tables of distributions
• Available for automated assignment
• Automatically generated
• With a single, distributed script
• From BMRB files

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Extensibility

• Python macro scripts
• Can be imported into the Analysis menu
• Embedded applications
• Format Converter, Clouds
• Use high-level function libraries
• Assignment, constraints, structure, molecules...
• Removes the need for detailed data model
  interaction
• Takes care of bookkeeping

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CcpNmr FormatConverter

• Imports and exports
• Sequences, peak lists, chemical shift lists,
  constraint lists, coordinates
• Fully or partly handles
• Ansig, CNS/XPLOR/ARIA, Diana/Dyana/Cyana, NMRStar
  (v2.1.1, v3.0), NmrView, Pdb, Pipp, Pronto,
  Sparky, XEasy
• Available and extensively tested
• Command line only
• Stand alone GUI
• Embedded in Analysis

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CcpNmr Clouds
Spectra
Pick Peaks, Link Shifts Combine
Pick Peaks Normalise

• An automated assignment and structure calculation
  strategy
• Based upon the spatial distribution of anonymous
  atoms generated with NOE information
• Implementation of existing software
• Interface existing code
• Re-written code modules
• Integration within CcpNmr
• An Analysis module
• Functional platform
• Distribution network
• Import/export with FormatConverter

Spin Systems
NOE intensities
Relaxation Matrix Optimisation
Distance Constraints
Hydrogen Atom Molecular Dynamics
Proton Clouds
Chain Fitting Molecular Replacement
Chain Assignment
Full Structure Calculation
Protein Structure
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URLs

• CCPN Web Site
• www.ccpn.ac.uk
• Data model documentation
• Software downloads
• Meeting information
• News and Discussion group
• www.jiscmail.ac.uk/ccpnmr
• Bug fixes
• Wish lists
• Notification of releases

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Acknowledgements

• CCPN team (University of Cambridge, UK)
• Rasmus Fogh (Data model and implementation)
• Wayne Boucher (CcpNmr Processing and Analysis)
• Tim Stevens (CcpNmr Analysis and Clouds)
• Ernest Laue
• MSD group (EBI, Cambridge, UK)
• Wim Vranken (CcpNmr FormatConverter)
• John Ionides (Data model)
• Anne Pajon (Protein production)
• Kim Henrick

Biotechnology and Biological Sciences Research
Council European Union, Quality of Life and
Management of Living Resources Grants