In the McLain group we are interested in the interplay between biological molecules in solutions (and as amorphous solids) on the atomic and molecular level from angstroms (Å; 10-10 metres) to 100s of angstroms.  Our research is multi-disciplinary and uses multiple experimental and computational techniques. Our primary techniques are neutron scattering techniques - Local Structural Neutron Diffraction (LSND) and small angle neutron scattering (SANS) to measure atomic and molecular structure in these disordered systems; and inelastic neutron scattering (INS) to measure the dynamics.   We also probe the structure of molecules using both solution and solid state NMR techniques.  Neutron scattering experiments are performed both at the ISIS Facility (STFC, UK) and the Institut Laue-Langevin (France).

These experimental measurements are complemented with computer modelling techniques molecular dynamics (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.  

Atomic and nanoscale interactions in membranes
Besides being barriers to retain the cell contents, membranes are also responsible for signal transduction between the inside and outside of cells acting as 'gate-keepers' for membrane traffic.  Membranes are comprised of many chemically distinguishable components and the types of molecules present in membranes greatly affect its properties.  The importance of understanding the composition of membranes and how this composition influences its biophysical properties is important and has implications for disease control, drug delivery, antimicrobial resistance, cell signalling and understanding the development of life itself.

Membranes are largely held together by non-covalent bonding (hydrogen bonds and van der Waals or 'hydrophobic') interactions between their constituent molecules where the nature of these interactions is due not only the molecules themselves but also to the intra- and extracellular environments. The interplay between hydrogen-bonding and hydrophobic forces are responsible for not only membrane structure but also its subsequent functions.

Our group is using neutron diffraction and NMR combined with computer simulation to measure model membrane environments to understand the structural interactions between membrane constituents.

Peptide and small molecule association and hydration

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 recognised 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 described above we are working to discover how association and folding takes place in peptides on an atomic length scale.

Recent investigations by us on the structure of 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) We 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 (see figure at right) 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.

We are also investigating the dynamics of these small peptides in solution using inelastic neutron scattering techniques and both DFT and MD simulations to compare with experimental measurements. 

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