Research Interests

Research Interests

We specialise in understanding the solution behaviour of biological macromolecules and their complexes. We do this by utilising a number of biophysical techniques to determine the solution shape of molecules and the strength, stoichiometry and architecture of the complexes they form. We collaborate widely and offer expertise in the application of our core methodologies including:

  • Analytical ultracentrifugation (AUC)
  • Small angle X-ray scattering (SAXS)
  • Small angle neutron scattering (SANS)
  • Hydrodynamic bead modelling (HBM)

Examples of our work are shown below.

Recent publication highlights

Above: Graphical abstract from Byron & Vestergaard (2015) illustrating interplay of biophysical methods in order to fully understand protein-protein interactions. Two proteins are interacting: one depicted as a purple ribbon with flexible N-termini & C-termini and one particularly flexible loop, the other as a dark orange ab initioSANS/SAXS bead model. Other colours are: red - measurable parameters; yellow - surface topology elucidated by AFM or cryo-EM; yellow-green/blue sphere pair - FRET labels; green - collision cross section (CCS) elucidated by IMS; aqua blue - water; pink - surface backbone H exchanged by D. Above: Figure 3C of Laine et al (2015) depicting a homology model for Plasmodium falciparum apicoplast E3 that reveals an extra anti-parallel β-strand at the position where human E3BP (E3-binding protein) interacts with E3; a parasite-specific feature that may be exploitable for drug discovery against PDC. Seven fleximers (coloured differently in the regions that were allowed to flex) are overlaid to illustrate the scope of conformational space explored by the models generated by discrete molecular dynamics modelling.

Left: Figure 1 of Rocco & Byron (2015) summarising hydrodynamic models generated from the atomic resolution structure of lysozyme 6lyz.pdb, (C). (A) Bead-shell model generated by HYDROPRO. (B) Tessellated model generated by BEST. (D) 5 Å AtoB US SOMO bead model. (E) Direct correspondence US SOMO SoMo bead model, with overlaps. (F) Same as in (E) after overlap removal. In (D), red and orange are exposed & buried beads, respectively. In (E) & (F) blue: main-chain; cyan: hydrophobic; magenta: non-polar; red: polar; yellow: basic; green: acidic; white: fused beads; orange: buried beads. 

In an additional paper Rocco & Byron (2015) analysed the comparative performance of these hydrodynamic modelling programs and observed that a combination of SoMo overlapping bead models (E) followed by Zeno computation produced optimal results, with a 0 % average error (range −4 to +4 %).

Right: Example of the use of SAXS to complement crystallographic data (taken from Grinter et al (2014)). (Top) analysis of conformational heterogeneity of pectocin M2 reveals compact and extended ensembles in solution. The distribution of solution ensembles (generated by discrete molecular dynamics simulations) selected by GAJOE (in red) from a pool of 5000 random conformers (in grey).  ‌
Right: The two distinct populations are consistent with the two crystallographic conformations of the molecule.  ‌