Overview

Extend-NMR is a European Sixth Framework project that aims to bring together software for macromolecular NMR into a single well-connected pipeline.

Project description

The Extend-NMR project is a collaboration between European NMR software developers who have collectively developed an NMR software suite to support functional and structural proteomics. The Extend-NMR software pipeline encompasses the NMR software process from data acquisition and processing through resonance assignment, analysis and structure determination to validation and finally database deposition. All of the software elements in the Extend-NMR pathway are linked via a single graphical user interface and all of the open-source elements are installable as a single computational package. The pipeline is designed to eliminate the difficulties that a user may have when moving between different software tasks, and enables the system to be used as a high-thoughput tool for structural and functional genomics. The individual elements of the Extend-NMR pipeline are as follows: TopSpin™ (Bruker BioSpin GmbH); Data acquisition and processing, MDD (Orekhov); Multiway decomposition processing of non-uniformly sampled spectra, PRODECOMP (Billeter); Processing high-dimensionality projection spectra, AUREMOL (Kalbitzer); Bayesian peak picking, CcpNmr (Laue/CCPN); NMR data pipeline, assignment software and data format conversion, ARIA (Nilges); Automated NOE assignment and structure calculation, ISD (Nilges/Rieping); Bayesian inferential structure calculation, HADDOCK (Bonvin); High-ambiguity macromolecular docking, CING (Vuister/Vriend); Macromolecular structure validation, Deposition (Henrick/PDBe); Streamlined deposition to PDB and BMRB, The tight connection between all of the software components in the Extend-NMR project has been made possible by using the CCPN software development infrastructure. CCPN provides a unifying platform for all NMR software by providing a comprehensive data model and corresponding computer libraries, in multiple programming languages, which describe all aspects of the NMR data pathway

Scientific Goals

The aim of this project is to develop novel computational tools that extend the scope of NMR spectroscopy and make possible functional and structural studies of larger proteins and biomolecular complexes. In particular, the aim is to collaboratively develop a well integrated software package that will facilitate programmes in functional and structural genomics, i.e.:

• The identification of interaction sites with other proteins, ligands and drugs; studies of the conformations of excited states; and studies of molecular dynamics.
• Structure determination of larger proteins and biomolecular complexes that are not amenable to crystallisation.

This project involves:

• The development of novel computational tools that allow rapid assignment of NMR spectra for studies of biomolecular interactions and dynamics by making optimal use of existing (in particular structural) information, i.e. the NMR equivalent of molecular replacement in X-ray crystallography.
• Extending the scope of NMR spectroscopy by developing novel tools that allow the calculation of structures without the need for prior spectral assignment.
• The development of improved tools for the identification and quantification of signals from NMR data.

These key scientific objectives are facilitated by the development and implementation of a series of computational algorithms involving Bayesian analysis, maximum entropy reconstruction, multi-dimensional decomposition principle component analysis, and statistical- and expert system based analysis tools.