Project members

1. Ernest Laue. Biochemistry department, University of Cambridge, Cambridge, UK.
2. Kim Henrick, Wim Vranken. EBI, Hinxton, Cambridge, UK.
3. Michael Nilges. Institut Pasteur, Paris, France.
4. Gert Vriend, Geerten Vuister. Radboud University, Nijmegen, the Netherlands.
5. Martin Billeter, Vladislav Orekhov. Göteborg University, Göteborg, Sweden.
6. Hans-Robert Kalbitzer. University of Regensburg, Regensburg, Germany.
7. Bruno Guigas. Bruker Biospin, Germany.
8. Alexandre Bonvin, University of Utrecht, Utrecht, the Netherlands.

Project description

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 develop a software package that will facilitate programmes in functional and structural genomics, i.e.:

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

This project involves:

(1) 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.
(2) Extending the scope of NMR spectroscopy by developing novel tools that allow the calculation of structures without the need for prior spectral assignment.
(3) 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. These algorithms are being implemented within a common software framework developed by the CCPN project, so that they can be flexibly employed in the development of the different tools. We are developing novel tools for the validation of structures and experimental results and mine databases for NMR and structural information crucial to the aims of the project.