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.