Exploring cryo-electron microscopy with molecular dynamics. (28th February 2022)

• Record Type: Journal Article
• Authors: Vant, John W.; Sarkar, Daipayan; Nguyen, Jonathan; Baker, Alexander T.; Vermaas, Josh V.; Singharoy, Abhishek
• Is Part Of: Biochemical Society transactions. Volume 50:Number 1(2022)
• Page Start: 569
• Page End: 581
• Publication Date: 2022-02-28
• Subjects: cryo-electron microscopy -- molecular dynamics -- molecular modeling; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20210485
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : 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.