The aim of this proposal 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 pa ckage 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) S tructure determination of larger proteins and biomolecular complexes that are not amenable to crystallisation. This project will involve: (1) The development of novel computational tools that allow rapid assignment of NMR spectra for studies of biomolecu lar 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 al low 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 will be facilitated by the developm ent 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 algor ithms will be 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 will develop novel tools for the validation of structures and experimental resul ts and mine databases for NMR and structural information crucial to the aims of the project.
Call for proposal
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