Structural and dynamical investigations of peptides, lipids and membranes from the atomic scale to the nanoscale
Co-workers: Sebastian Busch, Richard Gillams, Andrew Johnston, Nicola Steinke
Group research website: McLain Group
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.
- 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. Angewandte Chemie - International Edition, In press doi:10/1002/ange.201307657
- 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
- Foglia, F., Lawrence, M.J., Lorenz, C.D. and McLain, S.E. (2010) On the hydration of the phosphocholine headgroup in aqueous solution. J. Chem. Phys. 133, 145103.
- McLain, S.E., Soper, A.K., Diadone, I., Smith, J.C. and Watts, A.(2008) Charged based interactions between peptides observed as a dominant force for clustering in solution. Angew. Chem., Int. Ed., 47, 9059-9062.
- McLain, S.E., Soper, A.K., Terry, A.E. and Watts, A.(2007) Structure and hydration of L-proline in aqueous solutions. J. Phys. Chem. B, 111, 4568-4580.
Figure 1: Water around O5' and O5 hydrogens in cellobiose in water where O5' (non-reducing ring) shows much less hydration than the O5 reducing ring in solution. (O'Dell et al. PLoS ONE (2012))
Figure 2: Association of dipeptide glycyl-L-alanine molecules in water. The red crosses represent the oxygen atoms of the water molecules present (McLain, et al. Agnew Chem. 2008)
Group website: McLain group website