Molecular biology emerged in the 1940s with the goal of understanding biological activity at the molecular level. Since the discovery of the DNA double helix, structural biology has focused primarily on determining the precise atomic structure of molecules. However, conventional high-resolution techniques such as cryo-electron microscopy or X-ray crystallography provide only static snapshots. Although nuclear magnetic resonance and computer simulations incorporate the dynamic dimension, no experimental method allows for the direct observation of a single, isolated molecular structure.
The major challenge currently facing the field is therefore to precisely link structural dynamics to biological function. To achieve this, integrated structural biology now combines several experimental approaches, chemical data, and computational tools. In this context, high-speed atomic force microscopy stands out by enabling the direct, time-resolved visualization of macromolecular motion. Nevertheless, the link between the topography obtained through this dynamic microscopy and the underlying atomic structures has yet to be fully exploited.
This research project therefore aims to use the computational pipeline called AFM-Assembly to translate dynamic microscopy data into structural information. The work will involve adapting and optimizing this set of algorithms—which have already been validated on static images—to process large sets of dynamic data. The selected candidate will be responsible for modifying the code for this pipeline, which runs on Linux, requiring a basic understanding of Shell and C programming. Finally, the study will rely on high-performance computers as well as experimental data that is either already available or acquired in collaboration with specialists in Marseille.