Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Edited by Eva Nogales, University of California, Berkeley, CA, and approved December 1, 2020 (received for review August 18, 2020)
Article Figures & SI
Figures
- Fig. 1.
DeepTracer model determination pipeline. All-atom structure of multichain protein complexes is determined fully automatically solely from a cryo-EM map and amino acid sequence using the steps shown in the center of the figure. The structure shown on the right side is an actual model built by DeepTracer.
- Fig. 2.
Architecture of tailored convolutional neural network. Top shows overview of DeepTracer’s neural network architecture consisting of four parallel U-Nets. The gray boxes show the input and output maps, with their dimensions noted to the left and the number of channels marked below. Bottom dashed box shows the detailed architecture of each parallel U-Net. The blue boxes show the output maps of the different layers, where the dimensions of the maps are depicted on the left and the number of channels is depicted on top.
- Fig. 3.
Example masks from the training dataset based on the PDB ID code 6NQ1 deposited model structure. (A) Deposited model structure. (B) Backbone (Cα, C, and N atoms) in purple and side chains in green. (C) Atoms mask with labels for Cα, C, and N atoms. (D) Secondary structure mask with helices in turquoise, loops in pink, and sheets in orange. (E) Amino acid type mask with 20 different colors.
- Fig. 4.
Backbone confidence map of the EMD-0478 map with identified chains annotated in different colors.
- Fig. 5.
Traced backbone atoms. Predicted Cα atoms for the EMD-4054 map in blue before (Left) and after (Right) the backbone tracing step compared to the deposited model structure in pink.
- Fig. 6.
Protein sequence alignment algorithm. Interval of the predicted sequence is aligned with the target sequence using a custom dynamic algorithm. The amino acid confusion matrix depicts the relative frequency of pairs of predicted and true amino acid type and was calculated based on a set of test cryo-EM maps. The numbers shown in the score matrix are solely for illustrative purposes and do not reflect real data.
- Fig. 7.
Carbon, nitrogen, and oxygen determination. (A) Initial positioning of carbon (yellow) and nitrogen (blue) atoms in between the Cα atoms (gray) on Left and their initial refined positioning, which fits the U-Net prediction of carbon atoms (green volume) and nitrogen atoms (blue volume), on Right. (B) The positions of carbon and nitrogen atoms are refined further by forcing bond angles into their well-known values. The blue lines represent the bonds from the initial refinement. The red lines represent the bonds from the final refinement. (C) Position of oxygen atom in the carbonyl group by definition.
- Fig. 8.
Evaluation results for set of 476 experimental cryo-EM maps. Evaluation of determined models from DeepTracer (blue) and Phenix (red) for 476 cryo-EM maps. The dotted lines represent the trend for each method. DeepTracer outperformed Phenix in all four metrics. Precise data can be found in SI Appendix, Table S3.
- Fig. 9.
Results of EMD-6757 map. Models built by DeepTracer (blue) and Phenix (red) next to PDB ID code 5XS7 deposited model structure (yellow) for EMD-6757 map.
- Fig. 10.
Results of EMD-6272 map. Models built by DeepTracer (blue) and Phenix (red) compared to PDB ID code 3J9S deposited model structure (yellow) for EMD-6272 map. Top shows structures in ribbon view, and Bottom shows structures in all-atom view. Areas where DeepTracer correctly predicted amino acids that Phenix missed are highlighted by the four red circles.
- Fig. 11.
Results for coronavirus-related cryo-EM maps. Evaluation of models built by DeepTracer (blue) and Phenix (red) for 52 coronavirus-related high-resolution cryo-EM maps. The dotted lines represent the trend for each method. Computation times are shown on a logarithmic scale. Precise data can be found in SI Appendix, Table S2.
- Fig. 12.
Models built from SARS-CoV-2 cryo-EM maps, which do not have deposited model structures in the EMDR. DeepTracer model for the EMD-30044 map (Top) showing a human receptor ACE2 to which spike proteins of the SARS-CoV-2 virus bind and (Bottom) the EMD-21374 depicting a SARS-CoV-2 spike glycoprotein. No model structure has been deposited to the EMDataResource for the cryo-EM maps as of the date this paper is announced.
Tables
Percent matching rmsd Percent sequence ID GDC lr0.5em)4-5lr0.5em)6-7lr0.5em)8-9l)10-11 EMDB PDB Residues DT P DT P DT P DT P 21375 6vsb 2905 84.90 48.60 1.14 1.40 45.90 20.90 17.88 5.39 21452 6vxx 2916 91.40 53.80 0.96 1.18 61.30 40.00 — — 30039 6m17 3072 80.30 53.10 1.72 1.72 69.80 54.60 11.84 8.31 30127 6m71 1077 91.70 54.20 1.02 1.20 58.60 16.60 20.74 8.89 30178 7btf 1227 94.90 81.00 0.83 1.09 85.80 51.80 65.57 23.06 30209 7bv1 1102 87.60 67.00 0.84 1.29 87.50 30.50 55.62 18.15 30210 7bv2 1006 92.40 78.20 0.78 1.08 88.90 53.70 40.90 13.32 Average 89.03 62.27 1.04 1.28 71.11 38.30 35.42 12.85 GDC score could not be calculated for the EMD-21452 map, as the LGA web service could not process the modeled structures due to their size. EMDB, Electron Microscopy Data Bank.
Data supplements
Supporting Information
DeepTracer for fast de novo cryo-EM protein structure modeling and special studies on CoV-related complexes
Article Classifications
- Biological Sciences
- Biophysics and Computational Biology
- Physical Sciences
- Biophysics and Computational Biology
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Launched in 1977, Voyagers 1 and 2 are still helping to resolve past controversies even as they help spark a new one: the true shape of the heliosphere.
Image credit: NASA/JPL-Caltech.
Heavy hydrogen makes heavy water more dense and raises its boiling point. It also appears to affect another characteristic long rumored: taste.
Image credit: Shutterstock/sl_photo.
Jonathon Yuly, David Beratan, and Peng Zhang investigate how electron bifurcation reactions work.
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.