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While crystallography has been providing atomic-resolution structures of biomolecules for over half a century, the real challenge of today’s biophysicists is to correlate molecules’ structure and dynamics in solution with their function.
Small-angle scattering (SAS) is the fundamental techniques for structural studies of biological systems in solution.
Thanks to advances in instrumentation and data analysis software, Small-angle X-ray scattering (SAXS), complemented by other methods, is becoming very popular in structural biology. Over the years, a number of computational tools have been developed for the analysis of SAXS curves, calculation of theoretical profiles and low-resolution reconstruction of model shapes.
Many efforts have been spent to reduce the running time of these tools without degrading the quality of their approximations, most prominently the ATSAS package developed at EMBL Hamburg. Particularly, the Crysol program calculates a model SAXS profile to test a structural hypothesis of a SAXS experiment.
The number of Bio-SAXS publications exploded as a result of this effort. Comparatively, the lack of user-friendly analysis tools has hindered the development of Small Angle Neutron Scattering (SANS), more complex but providing more information. The overall research topic of the current project is to extend the state-of-the-art computational methods for small-angle (both SAXS and SANS) scattering experiments and to provide the algorithmic foundation to the upcoming single-molecule experimental techniques.
In particular, the practical aim of the project is the development of software tools with intuitive user-interaction feedback. Mathematically, the project will rely on the very efficient representation of the scattering profiles based on polynomial expansions of the scattering amplitudes using spherical harmonics. Structural optimization will be performed using the fast Fourier transform–accelerated techniques and the polynomial translation theorems and large collective structural motions using Normal Mode Analysis.
Three main axes of the proposed project are :
- (i) Molecular flexibility and the ways of modelling it;
- (ii) Algorithmic developments for new experimental setups, particularly combining SAXS and SANS data, and 2D scattering;
- (iii) Practical software development with intuitive user interfaces. Keywords: structural bioinformatics; integrative structural biology; small-angle scattering; Fourier analysis; polynomial expansions; spherical harmonics