EPSRC logo

Details of Grant 

EPSRC Reference: GR/S77639/01
Title: Development of an Ion Mobility Mass Spectrometer to Study Structure and Energetics of Proteins and Peptides
Principal Investigator: Barran, Professor PE
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Sch of Chemistry
Organisation: University of Edinburgh
Scheme: First Grant Scheme Pre-FEC
Starts: 28 June 2004 Ends: 27 June 2007 Value (£): 122,979
EPSRC Research Topic Classifications:
Biological & Medicinal Chem. Chemical Biology
Chemical Structure Instrumentation Eng. & Dev.
EPSRC Industrial Sector Classifications:
Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:  
Summary on Grant Application Form
The research proposed here will develop instrumentation to measure the rotationally averaged cross-section of proteins and peptides. This technique, Ion Mobility Mass Spectrometry (IM MS), is the gas phase equivalent of electrophoresis. Ions are injected into a cell filled with an inert buffer gas. The gas impedes their process, but they traverse the cell under the influence of a weak electrostatic field. Ions with a larger cross section undergo more collisions with helium and therefore spend a longer time drifting through the cell. The time taken for ions to reach a detector situated after the cell is proportional to the average collision cross section of the transmitted ions. Funds are sought to develop and upgrade existing instrumentation, specifically inserting a drift cell and related transfer optics into a tandem mass spectrometer. Part of this work will be performed in collaboration with MicroMass UK, and will facilitate a unique combination of instrumentation with which to examine gas phase structure. The IMMS will be used to study several species of direct biological relevance. To calibrate the instrumentation and determine the efficiency of using the IMMS as a high throughput device for the analysis of digested proteins, initial work will determine the cross section of small peptides. We will use the drift cell to measure water binding energies to selected peptides, which will provide insight into the differences between gas-phase and solution structures. This will be of particular relevance to proposed work looking at the structural differences of homologues of LHRH a deca peptide responsible for signalling in the human reproductive system. Subsequent investigations will focus on assessing structural changes of proteins on binding metals and/or target ligands. This work will have relevance to establishing the effects of 'unusual' metals, for example the influence of Mg(II) when bound to calcium binding proteins. In addition, we will explore the aggregation propensity of a range of anti-microbial peptides. Studies of the structure of smaller peptides will be supported with molecular mechanics based modelling. These early investigations whilst challenging in their own right, will also build up a repertoire of example systems that may be studied with IMMS.
Key Findings
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Potential use in non-academic contexts
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Description This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Date Materialised
Sectors submitted by the Researcher
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Project URL: http://www.barran.chem.ed.ac.uk/
Further Information:  
Organisation Website: http://www.ed.ac.uk