Topic description

This PhD project aims to develop advanced software solutions for cryo-electron microscopy (cryo-EM) data analysis, modeling conformational heterogeneity, and identifying optimal binding candidates, by integrating image analysis and docking across multiple structural states. The new tools will be validated through their application to VCP/p97 data, a key protein that plays a central role in cellular homeostasis by extracting and unfolding damaged or unwanted proteins for their degradation [1]. The project will build on the image analysis software MDSPACE, which produces detailed maps of the conformational states of biomolecular complexes from cryo-EM images [2,3].

MDSPACE will be used to obtain a detailed map of the conformational states of VCP/p97, induced by nucleotide binding and miniprotein engagement. In parallel, a new docking software, MDSPACEdock, will be developed to enable rapid docking of potential ligands across the full confo...