CCPN Status Report

1
CCPN Status Report

• Penrith, August 2008

2
CCPN People

• Cambridge (Biochemistry)?
• Ernest Laue
• Wayne Boucher
• Rasmus Fogh
• Tim Stevens
• Dan ODonovan
• Wolfgang Rieping
• Alan da Silva
• Darima Lamazhapova
• EBI (MSD), Hinxton
• Kim Henrick
• Wim Vranken
• Chris Penkett
• John Ionides

3
Disunified Software

• Every program does things its own way
• proprietary data formats.
• No provision for data exchange
• limited choice, and data loss.
• No provision for data harvesting
• lost and neglected data.
• No basis for task or code sharing
• you must keep re-inventing the wheel.
• Software pipelines require interoperability

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Code Generation Framework
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Data Modelling
Chain Code
Residue 3 letter code Seq number
Atom Name Element
Coordinate X Y Z
6
CCPN API v2 Developments

• Shared API generation scripts for all
  implementations
• Python XML, Java XML, Java SQL
• File storage
• Easier to move projects
• Complex data types
• SymmTracelessMatrix (e.g. for alignment tensor)
• Online upgrade server
• Migration of data from v1 to v2

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Upgrading Projects to v2
8
CCPN Data Model Additions

• Factorisation(PRODECOMP / MDD)?
• Shape matrices, component indices on peaks,
• Sparse sampling info
• Projection RefExperiments
• Peak splitting and projection peaks
• Improved assignment, peak clusters
• Isotope Labelling
• Standard labelling schemes (e.g. 1,3 13C
  glycerol)?
• Labelled molecules general or site-specific
• Simulation (preliminary)?
• Generic dynamics runs (parameters, energy terms,
  constraints, input and output structures)?
• Generic annealing protocols (time steps,
  temperatures, potentials, ...)?
• Chain symmetry for calculations
• Aligned media
• RDC constraints,
• alignment tensors on constraints lists

9
CcpNmr Software Status

• CcpNmr Format Converter
• Python GUI version updated to CCPN v2
• Web-based version ready for testing (Chris
  Spronk, Wim Vranken)?
• CcpNmr Analysis
• Ready for first v2 release
• More functionality going in...
• CNS ligand topology file generation
• Generates CNS topology files for ligands based
  upon AnteChamber (Alan Da Silva)?
• Developments to use AMBER forcefield with
  CNS/ARIA (Wolfgang Rieping)?

10
Analysis v2 Release Schedule

• 11th August First alpha test release
• Need volunteers for first phase testing!
• All equivalent v1 functionality present
• Some new features already
• October Beta release (potentially unstable)
• Incorporation of promised major v2 features
• RDC measurement
• Automated backbone assignment
• Semi-automated side chain system
• Extend-NMR integration ready for testing
• December Stable, tested release
• Cessation of v1 support
• Withdrawal of v1 software downloads
• Easy installation mechanisms

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Analysis v2 GUI
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Analysis v2 Functionality

• DANGLE
• Dihedral angle restraints from shifts
• Secondary structure
• Publication format chemical shifts
• Compressed peak annotations
• 3J HNH? analysis
• Measure couplings
• Make ? dihedral angle restraints
• Customisable residue codes
• Initialise root peaks system
• HSQC, HNCO resonances
• Curate NH2 peaks
• Isotopomer labelling functions
• Structure ensembles
• With alignment, throughout Analysis
• Further experimental details
• Probes, spectrometer instrumentation
• Chemical shift references

13
Dihedral Angles from Global Likelihood Estimates
14
Automatic Backbone Assignment
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Software Pipelines Using CCPN v2
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The Extend-NMR Pipeline
CcpNmr Analysis, Auremol
ISD, ARIA, HADDOCK

TopSpin, MDD, PRODECOMP
CING
CCPN Data Model
Reference Data Isotopes Nuclei Chemical
Compounds Chemical Shifts Experiment Prototypes
CcpNmr FormatConverter
NMRStar 3.1
Multiple Legacy Formats
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TopSpin, MDD, Prodecomp Spectra
Auremol Peak Picking Assignment
CcpNmr Analysis Spectrum visualisation Assignment
Extend-NMR
ARIA 2 NOE Assignment
HADDOCK Complexes
ISD Refinement Parameterisation
CING Validation
BMRB, wwPDB AutoDep Deposition
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Extend-NMRCCPN Partner Status

• Bruker TopSpin
• Writes basic CCPN projects Experiments,
  DataSources Peak Lists
• Gothenburg MDD
• Extended spectrum model. Demonstrated loading of
  usf3 XML reconstructed spectra
• Gothenburg Prodecomp
• Extended spectrum model. Working Python GUI
  demonstration CCPN v2 interface
• Regensburg Auremol
• Shown principle of using a PythonC interface to
  call scientific functions
• Paris ARIA2
• Existing CCPN interface updated, testing under v2
• Cambridge ISD
• Working Python GUI and CCPN v2 interface
• Utrecht HADDOCK
• Working Python GUI and CCPN v2 interface
• Nijmegen CING
• Import from CCPN working

19
CCPN Interface Schemes
Via FormatConverter
Application
Formatted File
Proprietary Memory
CCPN XML/SQL
In-memory conversion
Custom conversion
Application
Proprietary Model
CCPN Data Model
CCPN XML/SQL
Direct API access
Application
CCPN XML/SQL
CCPN Data Model CcpNmr Functions
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Integration Strategies Employed

• Direct Java Calls
• TopSpin
• Direct Python Calls
• ARIA
• ISD
• CING
• Prodecomp (Matlab ? NumPy)?
• File import/export (with Python GUI)?
• HADDOCK
• Python ? C layer
• Auremol

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Extend-NMR GUI HADDOCK
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Extend-NMR GUI Prodecomp
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Reduced dimensionality/projection spectra
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Extend-NMR GUI ISD
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ISD - Release 1.1

• ISD - Bayesian NMR structure calculation
• Full CCPN support
• Import Mol. system, NOEs, J couplings, torsion
  angles, H-bonds
• Export Probabilistic structure ensemble,
  auxiliary parameters (e.g. estimated RDC
  alignment tensor), project settings
• Launch ISD calculation directly from CCPN
  project
• Improved performance
• New analyses (e.g. NOE violation probabilities)
• Infrastructure (parallelisation, user interface,
  documentation)

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Solid State Data Through The CCPN Pipeline
ARIA2 Selecting CCPN Peaks and Isotope Scheme
CCPN Isotopomer Editor
Isotopomer Schemes
Solid Sate Structure
Peak Lists Assignments
Structure Restraints
ARIA / CCPN
ARIA CNS
CcpNmr Analysis
Spectra
Solid state Experiment Definitions
ARIA/CNS Structure
CCPN Solid state experiment prototypes
27
CING Integrated Validation Approach

• User friendly interface to WHAT IF, QUEEN,
  PROCHECK, SHIFTX reports.
• Residue oriented
• Validation and data together
• Hyperlinked HTML
• Color-coded (green, orange, red)
• Automated export to multiple formats
• API to data and validation results

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CING Data flow
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CING HTML Residue Oriented
Residue page
Links to home, up, previous,next residues
Restraints
f,? plot
Restraint limits
Data CV, scores, etc
?1,?2 plot
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PDBe/AutoDep

• Start with a CCPN project (needs to be API v2
  can use upgrade server if you have a v1 project)
• Add a BMRB Entry object to your project can
  use FormatConverter (and Analysis in the future)
• Send to EBI/PDBeAutoDep server
• This then gets curated by PDBe curators for
  structural information
• CCPN project gets updated with curated
  information
• Project gets written out in NMR-Star formatted
  and automatically gets sent to BMRB for curation
  of NMR data

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Documentation Projects

• Documentation Wiki for Analysis, integrated with
  in-program help. In progress
• Web version of FormatConverter with more friendly
  user interface. Ready to test
• Both contracted with Spronk Nmr Consultancy
  (Chris Spronk)?