Rishwanth Raghu will present his General Exam "Guiding protein diffusion models with cryo-EM imaging data" on Tuesday, May 5, 2026 at 10:00 AM in CS 302 and via zoom.
Rishwanth Raghu will present his General Exam "Guiding protein diffusion models with cryo-EM imaging data" on Tuesday, May 5, 2026 at 10:00 AM in CS 302 and via zoom. Zoom link: https://princeton.zoom.us/j/97312957225?pwd=3jz5x5tUukbWiHpmlC346C8GZHdYPb.1 Committee Members: Ellen Zhong (advisor), Ben Raphael, Mona Singh Abstract: Protein structure prediction models can accurately infer 3D molecular coordinates from amino acid sequence alone, but often struggle to capture the multiple structural states adopted by flexible biomolecules. In parallel, cryo-electron microscopy (cryo-EM) has emerged as a powerful tool for imaging near-native structural variability, but is challenged by arduous pipelines to go from raw experimental data to atomic structure. We present our work bridging the gap between these modalities, combining heterogeneous cryo-EM data with the rich biophysical priors learned by protein structure prediction models. Our method guides the diffusion sampling trajectory of a pretrained prediction model using constraints derived from cryo-EM density maps, driving samples towards conformational states consistent with experimental data. We demonstrate that this flexible inference-time approach allows us to build atomic structures into diverse cryo-EM maps across dynamic biomolecular systems including transporters and antibodies. Finally, we share ongoing work in scaling these approaches to model full ensembles of atomic structures from continuous distributions of density maps. Reading List: https://docs.google.com/document/d/1V1GfmvXZJwdSlDTkTSouDERQh7gRSW9yE5vL6gJK... Everyone is invited to attend the talk, and those faculty wishing to remain for the oral exam following are welcome to do so.
participants (1)
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CS Grad Department