PhD defense: Abigail Barclay

Computational modelling in structural biology: insights from small-angle scattering and molecular dynamics simulations.

The central theme of the thesis is the modelling of biomolecules, such as proteins and lipid structures, with an emphasis on small-angle scattering and a side of molecular dynamics simulations.  The thesis includes analytical models and computational tools to better exploit the amount of structural information that can be extracted from small-angle scattering data.  This includes a novel form factor-based modelling scheme designed especially for membrane proteins with disordered regions in a nanodisc environment, which can account for flexible domains alongside other structurally elaborate components.  Further, the thesis presents a model-refinement strategy for analysing data series specifically from SEC-SAXS experiments, demonstrated on phospholipid nanodisc samples.  The thesis also presents a comprehensive SAXS and SANS study on the interaction of α-synuclein and charged lipid vesicles, resulting in the deformation of the vesicles into other structures .  Finally, work on all-atom simulations of the transition state of amyloid fibrils by integrating the simulation with experimental ϕ -values will be shown.