Towards single molecule protein structures: ultrafast nanoscale x-ray scattering(£2.3 M from the Basic Technology Programme)One of the most significant current chemical problems is the in situ determination of the structure of large biologically important molecular assemblies, at the single molecule scale in order to correlate structure and function.
In a high profile, flagship project, awarded in the first round basic technology programme we are concentrating on the determination of ‘molecular shape’ by using the scattering of ultra-short pulses (10 fs) of soft (1-30 nm) x-ray pulses, to determine the shape of single large molecules in non-crystalline different environments, as isolated molecules and ultimately in water.
The x-rays are produced using ultra-fast laser technology together with high harmonic generation (HHG). Currently producing 108 photons/s of coherent x-rays around 20 nm, which are focussed to a 10 mm spot using a tapered fibre capillary. The highest intensity available in the world from such a coherent tabletop system together with focussing that is unique. We have recorded scattering and diffraction from a self assembled layer of 200 nm latex beads and are proceeding to enhance the sensitivity of the system. Results from our system have led to a very significant improvement in the understanding of the HHG process in a capillary.
An electro-spray & nano-spray system is being built to enable the study of isolated molecules in controlled amounts of solvent. The ultra-short pulses mean that the scattering occurs before the molecules have been damaged. Having obtained molecular shape information of, for example, protein complexes, molecular dynamics simulations will then be used to relate information derived on molecular shape length to their atomic structure.
A fibre pump laser system is being developed in collaboration with the ORC providing a future path to a highly compact laboratory instrument for soft x-ray scattering and microscopy.