Deciphering Protein Complex Structures from Cryo-electron Microscopy Maps using Deep Learning

Thesis (Master's)--University of Washington, 2020Information about macromolecular structure of protein complexes such as SARS-CoV-2, and related cellular and molecular mechanisms can assist the search for vaccines and drug development processes. To obtain such structural information, we present DeepTracer, a fully automatic deep learning-based method for fast de novo multi-chain protein complex structure determination from high-resolution cryo-electron microscopy (cryo-EM) density maps. We applied DeepTracer on a previously published set of 476 raw experimental density maps and compared the results with a current state of the art method. The residue coverage increased by over 30% using DeepTracer and the RMSD value improved from 1.29Ã to 1.18Ã . Additionally, we applied DeepTracer on a set of 62 coronavirus-related density maps, among them 10 with no deposited structure available in EMDataResource. We observed an average residue match of 84% with the deposited structures and an average RMSD of 0.93Ã . Additional tests with related methods further exemplify DeepTracer's competitive accuracy and efficiency of structure modeling. DeepTracer allows for exceptionally fast computations, making it possible to trace around 60,000 residues in 350 chains within only two hours. The web service is globally accessible at https://deeptracer.uw.edu