Research Interests: Biological Mass Spectrometry; Instrument and technique development; protein structure and interactions; HDX; proteomics; molecular modelling.

We use a combination of experimental gas phase techniques, molecular modelling and solution chemistry methods to interrogate conformations of proteins, peptides and other natural products.

We are interested in developing instrumentation, and aim to be system rather than technique led. A particular interest is to probe conformational changes that occur as an indicator of biological activity, for example [Ca]²⁺ binding to Calmodulin, defensins binding to saccharides, or cyclosporin binding to cyclophillin.

We have developed ion mobility mass spectrometry as a tool to investigate changes in protein and peptide conformation. This work is supported by molecular mechanics based calculations which supply candidate geometries to compare with those measured.

Some of our work is based on interrogating model systems, as we seek a general understanding of biological processes. However, strong collaborations with biological chemists and medical researchers, enable us to also examine 'real world' problems.

In collaboration with Waters UK, we have developed new instrumentation and techniques to investigate changes in protein conformation that occur in response to chemical or physical intervention. We also utilise computational tools, principally molecular mechanics, to evaluate protein and peptide structure.

We study some well characterized protein systems such as the Calcium Binding Protein Calmodulin and the immunophillin Cyclophillin. We have developed strategies for screening proteins against target ligands in collaboration with Professors Nick Turner (University of Manchester) and Malcolm Walkinshaw (University of Edinburgh). This work is now being extended via a proteomic approach. We also employ proteomics to examine the human 'spitome', as part of collaboration with Proctor and Gamble.

Another area of investigation is the structure activity relationship of a group of anti-microbial peptides known as β-defensins. This work is performed in conjunction with Dr's Dominic Campopiano (U of E) and Dorin (MRC-HGU) and Professor John Govan as well as Dr. Derek Macmillan (UCL) Dr. David Wales (University of Cambridge). Our endeavours in this area have been cemented by the award of a platform grant.

The final major area of investigation, uses gas-phase techniques, in particular Ion Mobility and molecular modeling, to evaluate structures of analogues of small peptides. This has most fruitfully been applied to examine GnRH (gonadotropin releasing hormone) in association with Professor Bob Millar (MRC-HRSU). We are not limited to gas-phase techniques, and have recently been exploring HD exchange methodologies to determine solution conformations for comparison with those derived in the gas-phase. Deuterium is used to probe the solvent exposed portions of the protein/or complex, and mass spectrometry to report on this via mass increase measurements.

SELECTED RECENT PUBLICATIONS

1. FT-ICR study of a covalently bound β-defensin dimer: Linking Structure to Activity; P.E. Barran, N. Polfer, J. Dorin, D. Campopiano, J. Am. Chem. Soc. Com. Submitted for publication
2. Sequential Hydration of Small Protonated Peptides; D.F. Liu T. Wyttenbach, P.E. Barran, M.T. Bowers, J. Am. Chem. Soc., Submitted for Publication
3. Solvation of peptides, oligonucleotides and small proteins: Energetics, structure and dynamics; M.T. Bowers, T. Wyttenbach T, P.E. Barran, Abstr. Pap. Am. Chem S, 2002, 223, 159-Anyl Part 1
4. Stable [Pb.(ROH)n]2+ complexes: softening the base to suit the Lewis acid; G. Akibo-Betts, P.E. Barran, L. Puskar B. Duncombe, H. Cox, and A.J. Stace, J. Am. Chem. Soc. 2002, 124 (31), 9257-9264