Single particle analysis cryo-electron microscopy (EM) and molecular dynamics (MD) have been complimentary methods since cryo-EM was first applied to the field of structural biology. The relationship started by biasing structural models to fit low-resolution cryo-EM maps of large macromolecular complexes not amenable to crystallization. The connection between cryo-EM and MD evolved as cryo-EM maps improved in resolution, allowing advanced sampling algorithms to simultaneously refine backbone and sidechains. Moving beyond a single static snapshot, modern inferencing approaches integrate cryo-EM and MD to generate structural ensembles from cryo-EM map data or directly from the particle images themselves. We summarize the recent history of MD innovations in the area of cryo-EM modeling. The merits for the myriad of MD based cryo-EM modeling methods are discussed, as well as, the discoveries that were made possible by the integration of molecular modeling with cryo-EM. Lastly, current challenges and potential opportunities are reviewed.
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February 2022
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Cover Image
Cover Image
The highly conserved enzyme IMPDH plays an essential role in purine biosynthesis and is tightly regulated by many different mechanisms. Depicted here are cryo-EM structures of the large retinal splice variant of IMPDH1 in different filament assembly conformations overlaid on a cryo-EM micrograph of IMPDH1 filaments. Cover artwork created by Jesse Hansen.
Review Article|
February 25 2022
Exploring cryo-electron microscopy with molecular dynamics
John W. Vant
;
John W. Vant
1Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA
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Daipayan Sarkar
;
Daipayan Sarkar
1Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA
2MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
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Jonathan Nguyen
;
Jonathan Nguyen
1Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA
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Alexander T. Baker
;
Alexander T. Baker
1Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA
3Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA
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Josh V. Vermaas
;
Josh V. Vermaas
2MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
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Abhishek Singharoy
1Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA
Correspondence: Abhishek Singharoy (asinghar@asu.edu)
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Publisher: Portland Press Ltd
Received:
December 10 2021
Revision Received:
January 31 2022
Accepted:
February 02 2022
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem Soc Trans (2022) 50 (1): 569–581.
Article history
Received:
December 10 2021
Revision Received:
January 31 2022
Accepted:
February 02 2022
Citation
John W. Vant, Daipayan Sarkar, Jonathan Nguyen, Alexander T. Baker, Josh V. Vermaas, Abhishek Singharoy; Exploring cryo-electron microscopy with molecular dynamics. Biochem Soc Trans 28 February 2022; 50 (1): 569–581. doi: https://doi.org/10.1042/BST20210485
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