Exploring cryo-electron microscopy with molecular dynamics

Vant, John W.; Sarkar, Daipayan; Nguyen, Jonathan; Baker, Alexander T.; Vermaas, Josh V.; Singharoy, Abhishek

doi:10.1042/bst20210485

Title: Exploring cryo-electron microscopy with molecular dynamics

Journal Article · Fri Feb 25 00:00:00 EST 2022 · Biochemical Society Transactions

DOI:https://doi.org/10.1042/bst20210485· OSTI ID:1978924

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Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA
Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA; MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85281, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA
MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA

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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Research Organization:: Michigan State Univ., East Lansing, MI (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

DOE Contract Number:: FG02-91ER20021

OSTI ID:: 1978924

Journal Information:: Biochemical Society Transactions, Vol. 50, Issue 1; ISSN 0300-5127

Publisher:: Portland Press

Country of Publication:: United States

Language:: English

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MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG Williams, Christopher J.; Headd, Jeffrey J.; Moriarty, Nigel W. Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3330	journal	November 2017
EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy Barad, Benjamin A.; Echols, Nathaniel; Wang, Ray Yu-Ruei Nature Methods, Vol. 12, Issue 10 https://doi.org/10.1038/nmeth.3541	journal	August 2015

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