Deep Learning to Predict Protein Backbone Structure from High-Resolution Cryo-EM Density Maps.

Scientific Reports
Dong SiJianlin Cheng

Abstract

Cryo-electron microscopy (cryo-EM) has become a leading technology for determining protein structures. Recent advances in this field have allowed for atomic resolution. However, predicting the backbone trace of a protein has remained a challenge on all but the most pristine density maps (<2.5 Å resolution). Here we introduce a deep learning model that uses a set of cascaded convolutional neural networks (CNNs) to predict Cα atoms along a protein's backbone structure. The cascaded-CNN (C-CNN) is a novel deep learning architecture comprised of multiple CNNs, each predicting a specific aspect of a protein's structure. This model predicts secondary structure elements (SSEs), backbone structure, and Cα atoms, combining the results of each to produce a complete prediction map. The cascaded-CNN is a semantic segmentation image classifier and was trained using thousands of simulated density maps. This method is largely automatic and only requires a recommended threshold value for each protein density map. A specialized tabu-search path walking algorithm was used to produce an initial backbone trace with Cα placements. A helix-refinement algorithm made further improvements to the α-helix SSEs of the backbone trace. Finally, a novel qual...Continue Reading

References

Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Dec 25, 2002·Acta Crystallographica. Section D, Biological Crystallography·Thomas C Terwilliger
Jun 26, 2003·Nucleic Acids Research·Adam Zemla
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Apr 26, 2005·Nucleic Acids Research·Yang Zhang, Jeffrey Skolnick
Jan 31, 2006·Physiology·Liguo Wang, Fred J Sigworth
Jul 25, 2006·Journal of Structural Biology·Guang TangSteven J Ludtke
Jan 16, 2008·Journal of Computational Chemistry·Piotr Rotkiewicz, Jeffrey Skolnick
Jul 16, 2009·Proteins·Georgii G KrivovRoland L Dunbrack
Feb 25, 2010·Acta Crystallographica. Section D, Biological Crystallography·Thomas C Terwilliger
Feb 25, 2010·Acta Crystallographica. Section D, Biological Crystallography·Thomas C Terwilliger
Sep 17, 2013·Structure·Yifan SongDavid Baker
Dec 30, 2014·Trends in Biochemical Sciences·Xiao-chen BaiSjors H W Scheres
Feb 24, 2015·Nature Methods·Ray Yu-Ruei WangFrank DiMaio
May 23, 2015·Molecular Cell·Eva Nogales, Sjors H W Scheres
May 29, 2015·Nature·Yann LeCunGeoffrey Hinton
Oct 6, 2015·Nature·Richard K HiteRoderick MacKinnon
Apr 5, 2016·Scientific Reports·Renzhi Cao, Jianlin Cheng
May 31, 2016·Cell·Alan MerkSriram Subramaniam
Jan 24, 2017·Cell·Richard K Hite, Roderick MacKinnon
Oct 17, 2017·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Albert Ng, Dong Si
Apr 25, 2018·Nature Communications·Genki Terashi, Daisuke Kihara
May 15, 2018·Structure·Alberto BartesaghiSriram Subramaniam
Jun 7, 2018·Acta Crystallographica. Section D, Structural Biology·Thomas C TerwilligerPaul D Adams
Mar 22, 2019·Proceedings of the National Academy of Sciences of the United States of America·Kaiming ZhangWah Chiu
Feb 14, 2020·BioRxiv : the Preprint Server for Biology·J. Pfab, Dong Si

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Citations

Apr 16, 2020·Frontiers in Bioengineering and Biotechnology·Zi-Mei ZhangHao Lin
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Ting LiuHua Tang
Jan 1, 2021·The Journal of Chemical Physics·Justin T Seffernick, Steffen Lindert
Dec 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jonas PfabDong Si
Nov 25, 2020·Molecular Therapy. Nucleic Acids·Balachandran ManavalanGwang Lee
Mar 30, 2021·Expert Opinion on Drug Discovery·José Jiménez-LunaGisbert Schneider
May 7, 2021·Briefings in Bioinformatics·Jiahua He, Sheng-You Huang
Jun 3, 2021·International Journal of Molecular Sciences·Subash C PakhrinDukka B Kc
Sep 28, 2021·Journal of Chemical Information and Modeling·Mosavverul Hassan, Evangelos A Coutsias
Nov 25, 2020··Renzhi CaoSola Gbenro

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Software Mentioned

Rosetta
score
Pulchra
TensorFlow
Segnet
TM
Qprob
MAINMAST
CNN
EMAN2

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