Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
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Sylvia McLain
Structural and dynamical investigations of peptides, lipids and membranes from the atomic scale to the nanoscale

Co-workers:  Dr. Richard Gillams, Dr. Natasha Rhys (from Nov 2015), Mr. Andrew Johnston, Ms. Nicola Steinke, Mr. Christopher Sowden, PhD studentship available (Deadline November 2015) - apply here

Group research website: McLain Group website

We are interested in understanding the interactions between biological molecules at the atomic level in physiologically relevant environments. We use a combination of neutron scattering, NMR and computer simulation to probe the interplay between these molecules on the atomic and molecular level (Å (10-10 metres)) to the nanoscale (10-9metres).  

Currently we are focusing on understanding the interactions between membrane constituents using two experimental techniques - local structural neutron diffraction (LSND) and high resolution NMR. Determination of the organisation of model membranes in solution and as amorphous solids allows for a direct comparison between the structure under both of these conditions. This is important because many membranes and membrane constituents are sparingly soluble in water. These experimental measurements are complemented with computer modelling techniques (MD and Empirical Potential Structure Refinement (EPSR)) to investigate how the atomic scale structure and dynamics link to larger structures on the nanometre length scale.

We are also interested in the principles and processes by which proteins assemble from amino acid chains into biologically functional three-dimensional structures.

 This has long been recognized to be one of the major challenges spanning the physical and life sciences. To date, there is little information which links interactions between water and biological molecules on the atomic length scale with how nature engineers larger structures. Using the same range of techniques we aim to discover how association and folding takes place in peptides on an atomic length scale.

Investigations by us on dipeptides addressed the hydrophobic versus the hydrophilic nature of association between peptide fragments in solution (McLain, SE, et al. (2008) Agnew. Chem. 47, 9059-9062). It was found that electrostatic interactions were dominant to hydrophobic association in the presence of water, converse to previous claims that the driving force for assembly is due to hydrophobic clustering in small systems. Not only were charged interactions found to prevail between these small peptides, but the most ’hydrophobic’ peptides associated with each other the least whilst the most hydrophilic peptides showed the most association (figure below) both by virtue of charge-charge association and by their hydrophobic-hydrophobic association. This leads to a hypothesis that charged portions of peptide chains may guide hydrophobic groups towards association and this may be one of the keys to understanding protein folding and assembly.

Recent Publications

  1. Gillams, R. J., Busto, J. V., Busch, S., Goñi, F. M., Lorenz, C. D. and McLain, S. E. (2015) Solvation and hydration of the ceramide headgroup in a non-polar solution. J. Phys. Chem. B, 119 (1) 128-135. doi:10.1021/jp5107789
  2. Busch, S., Lorenz, C.D., Taylor, J.W., Pardo, L.C. and McLain, S.E. (2014) Short range interactions of concentrated proline in aqueous solution.  J. Phys. Chem. B., 118 (49), 14267-14277. doi: 10.1021/jp508779d
  3. Busch, S., Bruce, C.D.,Redfield, C., Lorenz, C.D. and McLain, S.E. (2013)  Water mediation essential to nucleation of ß-turn formation in peptide folding motifs. Angew. Chem. Int. Ed., 52 (49), 13091 - 13095.  doi:10/1002/ange.201307657
  4. Busch, S., Pardo, L.C., Redfield, C., Lorenz, C.D. and McLain, S.E. (2013) On the structure of water and chloride ion interactions with a peptide backbone in solution. Phys. Chem. Chem. Phys., 15, 21023-21033. doi:10.1039/C3CP5831A
  5. O'Dell, W.B., Baker, D.C. and McLain, S.E. (2012) Structural Evidence for Inter-residue Hydrogen Bonding Observed for Cellobiose in Aqueous Solution PLoS One 7(10): e45311.  doi:10.1371/journal.pone.0045311
Full publication list...

Research Images

Water-mediation observed to be essential to the nucleation of ß-turn formation for peptides in solution.  The figure shows representative water-mediated turns for the peptide glycine-proline-glycinamide (GPG) in aqueous solution.  The red dotted line represents water mediated turns observed from computer simulations of neutron diffraction data and the blue line represents water-mediated turns from MD simulations.   (S. Busch, et al. Agnew. Chem. Int. Ed. (2013))

Water-mediated ceramide head group interactions for ceramide and water in a non-polar solution showing a water molecule simultaneously bound to both the carbonly of the amide group and a hydroxyl group. (RJ Gillams et al. J. Phys. Chem, B (2015))

Positions available: PhD Studentship starting January 2016 (Deadline Nov 13, 2015) - apply here

Group website: McLain group website