Award details

Enhanced computing infrastructure for structural biology and bioinformatics at the University of Leeds

Reference	REI20490
Principal Investigator / Supervisor	Professor Neil Ranson
Co-Investigators / Co-Supervisors	Professor Steve Homans, Dr Richard Jackson, Dr Joachim Jaeger, Professor Peter Knight, Professor Simon Phillips, Professor Nicola Jane Stonehouse, Professor John Trinick, Professor David Westhead
Institution	University of Leeds
Department	Inst of Molecular & Cellular Biology
Funding type	Research
Value (£)	197,958
Status	Completed
Type	Research Grant
Start date	01/01/2004
End date	31/01/2005
Duration	13 months

Abstract

The objective of this proposal is to establish a state-of-the-art high performance computing resource, consisting of integrated processing, storage and archival facilities, for Structural Biology and Bioinformatics at the University of Leeds. Structural biology and bioinformatics play an increasingly central role in modern molecular biology, providing crucial insights into the function of biological macromolecules. The range and scope of such research undertaken at Leeds is very broad and strong collaborations exist between the research groups to facilitate an integrated approach to reconciling structure with function at all resolutions; from gross conformational change in macromolecular complexes down to the atomic detail of molecular recognition events. Electron microscopy at Leeds is investigating conformational change and force generation in molecular motors such as myosin and dyenein, and how conformational change is harnessed to function in macromolecular machines such as the chaperone/protease ClpAp and the molecular chaperone GroEL. In close collaboration with X-ray crystallography and NMR, we are also investigating the role of exocyst complex in tethering secretory vesicles to the plasma membrane. The resolution attainable using cryo-electron microscopy and single particle image processing is already well in excess of 10 Angstrom and continues to improve dramatically. However, this improvement requires computational resources far beyond those available through project grant support. At atomic resolution, strong contributions are being made by both NMR and x-ray crystrallography. NMR research continues to focus on the structure determination of a number of medically interesting target proteins, but is also moving increasingly into a calculating per-residue entropies from NMR relaxation data. These per-residue entropy calculations are vital for understanding the dynamics and thermodynamics of protein-ligand interactions, and thus are crucial to rational drugdesign. However, their calculation requires extended molecular dynamics simulations. There is an extremely strong program of X-ray crystallography at the University of Leeds, working on a wide range of systems, but with a particular strength in protein-nucleic acid interactions. Cutting edge techniques such as the use of viral capsids as supra-molecular scaffolds for crystallisation of different targets, increasing use of crystallisation robots and MAD data collection are dramatically increasing their computational requirements for structure determination. The growing bioinformatics research group is developing methods to employ structural information in genomics and proteomics, and for the analysis of structural genomics data. Projects under development include protein-protein and protein-ligand docking procedures, machine learning and metabolic reconstruction.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Research Equipment Initiative 2003 (RE2) [2003]
Funding Scheme	X – not Funded via a specific Funding Scheme

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