Zoom Link: https://mit.zoom.us/j/93513735220
Title: Machine Learning for Determining Protein Structure and Dynamics from Cryo-EM Images
Major technological advances in cryo-electron microscopy (cryo-EM) have produced new opportunities to study the structure and dynamics of proteins and other biomolecular complexes. However, this structural heterogeneity complicates the algorithmic task of 3D reconstruction from the collected dataset of 2D cryo-EM images. In this seminar, I will overview cryoDRGN and related methods that leverage the representation power of deep neural networks for cryo-EM reconstruction. Underpinning the cryoDRGN method is a deep generative model parameterized by an implicit neural representation of 3D volumes and a learning algorithm to optimize this representation from unlabeled 2D cryo-EM images. Extended to real datasets and released as an open-source tool, these methods have been used to discover new protein structures and visualize continuous trajectories of protein motion. I will discuss various extensions of the method for scalable and robust reconstruction, analyzing the learned generative model, and visualizing dynamic protein structures in situ.
Ellen Zhong is an Assistant Professor of Computer Science at Princeton University. She is interested in problems at the intersection of AI and biology. Her research develops machine learning methods for computational and structural biology problems with a focus on protein structure determination with cryo-electron microscopy (cryo-EM). She obtained her Ph.D. from MIT in 2022, advised by Bonnie Berger and Joey Davis, where she developed deep learning algorithms for 3D reconstruction of dynamic protein structures from cryo-EM images. She has interned at DeepMind with John Jumper and the AlphaFold team and previously worked on molecular dynamics algorithms and infrastructure for drug discovery at D. E. Shaw Research. She obtained her B.S. from the University of Virginia where she worked with Michael Shirts on computational methods for studying protein folding.