{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T08:33:31Z","timestamp":1793694811275,"version":"4.5.1"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1038\/s41594-022-00734-6","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T11:06:27Z","timestamp":1646737587000},"page":"250-260","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication\u2013transcription complex"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-003X","authenticated-orcid":false,"given":"James","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7752-9824","authenticated-orcid":false,"given":"Brandon","family":"Malone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza","family":"Llewellyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3170-1622","authenticated-orcid":false,"given":"Yakov","family":"Pechersky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashyap","family":"Maruthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8014-7269","authenticated-orcid":false,"given":"Ed T.","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5492-0652","authenticated-orcid":false,"given":"Jason K.","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-5761","authenticated-orcid":false,"given":"David E.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-3153","authenticated-orcid":false,"given":"Seth A.","family":"Darst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"734_CR1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","volume":"579","author":"F Wu","year":"2020","unstructured":"Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265\u2013269 (2020).","journal-title":"Nature"},{"key":"734_CR2","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270\u2013273 (2020).","journal-title":"Nature"},{"key":"734_CR3","doi-asserted-by":"publisher","first-page":"E3900","DOI":"10.1073\/pnas.1323705111","volume":"111","author":"L Subissi","year":"2014","unstructured":"Subissi, L. et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc. Natl Acad. Sci. USA 111, E3900\u2013E3909 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"734_CR4","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1038\/s41467-019-10280-3","volume":"10","author":"RN Kirchdoerfer","year":"2019","unstructured":"Kirchdoerfer, R. N. & Ward, A. B. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat. Commun. 10, 2342\u20132349 (2019).","journal-title":"Nat. Commun."},{"key":"734_CR5","doi-asserted-by":"publisher","unstructured":"Hillen, H. S. et al. Structure of replicating SARS-CoV-2 polymerase. Nature https:\/\/doi.org\/10.1038\/s41586-020-2368-8 (2020).","DOI":"10.1038\/s41586-020-2368-8"},{"key":"734_CR6","doi-asserted-by":"publisher","first-page":"6785","DOI":"10.1074\/jbc.RA120.013679","volume":"295","author":"CJ Gordon","year":"2020","unstructured":"Gordon, C. J. et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J. Biol. Chem. 295, 6785\u20136797 (2020).","journal-title":"J. Biol. Chem."},{"key":"734_CR7","doi-asserted-by":"publisher","first-page":"16156","DOI":"10.1074\/jbc.AC120.015720","volume":"295","author":"EP Tchesnokov","year":"2020","unstructured":"Tchesnokov, E. P. et al. Template-dependent inhibition of coronavirus RNA-dependent RNA polymerase by remdesivir reveals a second mechanism of action. J. Biol. Chem. 295, 16156\u201316165 (2020).","journal-title":"J. Biol. Chem."},{"key":"734_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20542-0","volume":"12","author":"G Kokic","year":"2021","unstructured":"Kokic, G. et al. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nat. Commun. 12, 279 (2021).","journal-title":"Nat. Commun."},{"key":"734_CR9","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/bs.aivir.2016.08.008","volume":"96","author":"EJ Snijder","year":"2016","unstructured":"Snijder, E. J., Decroly, E. & Ziebuhr, J. The nonstructural proteins directing coronavirus RNA synthesis and processing. Adv. Virus Res. 96, 59\u2013126 (2016).","journal-title":"Adv. Virus Res."},{"key":"734_CR10","doi-asserted-by":"publisher","first-page":"5213","DOI":"10.1128\/JVI.74.11.5213-5223.2000","volume":"74","author":"LC van Dinten","year":"2000","unstructured":"van Dinten, L. C., van Tol, H., Gorbalenya, A. E. & Snijder, E. J. The predicted metal-binding region of the arterivirus helicase protein is involved in subgenomic mRNA synthesis, genome replication, and virion biogenesis. J. Virol. 74, 5213\u20135223 (2000).","journal-title":"J. Virol."},{"key":"734_CR11","doi-asserted-by":"publisher","first-page":"9586","DOI":"10.1128\/JVI.74.20.9586-9593.2000","volume":"74","author":"A Seybert","year":"2000","unstructured":"Seybert, A., Dinten, L. C., van, Snijder, E. J. & Ziebuhr, J. Biochemical characterization of the equine arteritis virus helicase suggests a close functional relationship between arterivirus and coronavirus helicases. J. Virol. 74, 9586\u20139593 (2000).","journal-title":"J. Virol."},{"key":"734_CR12","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1128\/JVI.79.2.696-704.2005","volume":"79","author":"A Seybert","year":"2005","unstructured":"Seybert, A. et al. A complex zinc finger controls the enzymatic activities of nidovirus helicases. J. Virol. 79, 696\u2013704 (2005).","journal-title":"J. Virol."},{"key":"734_CR13","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.virusres.2014.12.001","volume":"202","author":"KC Lehmann","year":"2015","unstructured":"Lehmann, K. C., Snijder, E. J., Posthuma, C. C. & Gorbalenya, A. E. What we know but do not understand about nidovirus helicases. Virus Res. 202, 12\u201332 (2015).","journal-title":"Virus Res."},{"key":"734_CR14","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.cell.2009.03.036","volume":"137","author":"K Saikrishnan","year":"2009","unstructured":"Saikrishnan, K., Powell, B., Cook, N. J., Webb, M. R. & Wigley, D. B. Mechanistic basis of 5\u2032\u22123\u2032 translocation in SF1B helicases. Cell 137, 849\u2013859 (2009).","journal-title":"Cell"},{"key":"734_CR15","doi-asserted-by":"publisher","first-page":"e36521","DOI":"10.1371\/journal.pone.0036521","volume":"7","author":"AO Adedeji","year":"2012","unstructured":"Adedeji, A. O. et al. Mechanism of nucleic acid unwinding by SARS-CoV helicase. PLoS ONE 7, e36521 (2012).","journal-title":"PLoS ONE"},{"key":"734_CR16","doi-asserted-by":"publisher","unstructured":"Mickolajczyk, K. J. et al. Force-dependent stimulation of RNA unwinding by SARS-CoV-2 nsp13 helicase. Biophys. J. https:\/\/doi.org\/10.1016\/j.bpj.2020.11.2276 (2020).","DOI":"10.1016\/j.bpj.2020.11.2276"},{"key":"734_CR17","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1146\/annurev.biochem.76.052305.115300","volume":"76","author":"MR Singleton","year":"2007","unstructured":"Singleton, M. R., Dillingham, M. S. & Wigley, D. B. Structure and mechanism of helicases and nucleic acid translocases. Annu. Rev. Biochem. 76, 23\u201350 (2007).","journal-title":"Annu. Rev. Biochem."},{"key":"734_CR18","doi-asserted-by":"publisher","first-page":"e1006474","DOI":"10.1371\/journal.ppat.1006474","volume":"13","author":"W Hao","year":"2017","unstructured":"Hao, W. et al. Crystal structure of Middle East respiratory syndrome coronavirus helicase. PLoS Pathog. 13, e1006474 (2017).","journal-title":"PLoS Pathog."},{"key":"734_CR19","doi-asserted-by":"publisher","first-page":"6538","DOI":"10.1093\/nar\/gkz409","volume":"47","author":"Z Jia","year":"2019","unstructured":"Jia, Z. et al. Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic Acids Res. 47, 6538\u20136550 (2019).","journal-title":"Nucleic Acids Res."},{"key":"734_CR20","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1016\/j.cell.2020.07.033","volume":"182","author":"J Chen","year":"2020","unstructured":"Chen, J. et al. Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication\u2013transcription complex. Cell 182, 1560\u20131573.e13 (2020).","journal-title":"Cell"},{"key":"734_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19770-1","volume":"11","author":"L Yan","year":"2020","unstructured":"Yan, L. et al. Architecture of a SARS-CoV-2 mini replication and transcription complex. Nat. Commun. 11, 5874 (2020).","journal-title":"Nat. Commun."},{"key":"734_CR22","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.cell.2020.11.016","volume":"184","author":"L Yan","year":"2021","unstructured":"Yan, L. et al. Cryo-EM structure of an extended SARS-CoV-2 replication and transcription complex reveals an intermediate state in cap synthesis. Cell 184, 184\u2013193.e10 (2021).","journal-title":"Cell"},{"key":"734_CR23","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.coviro.2021.03.010","volume":"48","author":"HS Hillen","year":"2021","unstructured":"Hillen, H. S. Structure and function of SARS-CoV-2 polymerase. Curr. Opin. Virol. 48, 82\u201390 (2021).","journal-title":"Curr. Opin. Virol."},{"key":"734_CR24","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.1093\/nar\/gkt1310","volume":"42","author":"Z Deng","year":"2013","unstructured":"Deng, Z. et al. Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase. Nucleic Acids Res. 42, 3464\u20133477 (2013).","journal-title":"Nucleic Acids Res."},{"key":"734_CR25","doi-asserted-by":"publisher","unstructured":"Tavares, R. et al. The global and local distribution of RNA structure throughout the SARS-CoV-2 Genome. J. Virol. https:\/\/doi.org\/10.1128\/JVI.02190-20 (2021).","DOI":"10.1128\/JVI.02190-20"},{"key":"734_CR26","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.molcel.2020.12.041","volume":"81","author":"NC Huston","year":"2021","unstructured":"Huston, N. C. et al. Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms. Mol. Cell 81, 584\u2013598.e5 (2021).","journal-title":"Mol. Cell"},{"key":"734_CR27","doi-asserted-by":"publisher","first-page":"e2102516118","DOI":"10.1073\/pnas.2102516118","volume":"118","author":"B Malone","year":"2021","unstructured":"Malone, B. et al. Structural basis for backtracking by the SARS-CoV-2 replication\u2013transcription complex. Proc. Natl Acad. Sci. USA 118, e2102516118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"734_CR28","doi-asserted-by":"crossref","unstructured":"Seifert, M. et al. Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective. eLife e70968 (2021).","DOI":"10.7554\/eLife.70968"},{"key":"734_CR29","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","volume":"180","author":"SHW Scheres","year":"2012","unstructured":"Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519\u2013530 (2012).","journal-title":"J. Struct. Biol."},{"key":"734_CR30","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.jsb.2013.08.002","volume":"184","author":"G Cardone","year":"2013","unstructured":"Cardone, G., Heymann, J. B. & Steven, A. C. One number does not fit all: mapping local variations in resolution in cryo-EM reconstructions. J. Struct. Biol. 184, 226\u2013236 (2013).","journal-title":"J. Struct. Biol."},{"key":"734_CR31","doi-asserted-by":"publisher","first-page":"e11182","DOI":"10.7554\/eLife.11182","volume":"4","author":"X Bai","year":"2015","unstructured":"Bai, X., Rajendra, E., Yang, G., Shi, Y. & Scheres, S. H. W. Sampling the conformational space of the catalytic subunit of human \u03b3-secretase. eLife 4, e11182 (2015).","journal-title":"eLife"},{"key":"734_CR32","doi-asserted-by":"publisher","first-page":"3474","DOI":"10.1016\/j.cell.2021.05.033","volume":"184","author":"L Yan","year":"2021","unstructured":"Yan, L. et al. Coupling of N7-methyltransferase and 3\u2032\u22125\u2032 exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading. Cell 184, 3474\u20133485.e11 (2021).","journal-title":"Cell"},{"key":"734_CR33","doi-asserted-by":"publisher","first-page":"4848","DOI":"10.1038\/s41467-021-25166-6","volume":"12","author":"JA Newman","year":"2021","unstructured":"Newman, J. A. et al. Structure, Mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase. Nat. Commun. 12, 4848\u20134858 (2021).","journal-title":"Nat. Commun."},{"key":"734_CR34","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.molcel.2011.02.010","volume":"41","author":"S Chakrabarti","year":"2011","unstructured":"Chakrabarti, S. et al. Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2. Mol. Cell 41, 693\u2013703 (2011).","journal-title":"Mol. Cell"},{"key":"734_CR35","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/sj.emboj.7601464","volume":"26","author":"Z Cheng","year":"2007","unstructured":"Cheng, Z., Muhlrad, D., Lim, M. K., Parker, R. & Song, H. Structural and functional insights into the human Upf1 helicase core. EMBO J. 26, 253\u2013264 (2007).","journal-title":"EMBO J."},{"key":"734_CR36","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1021\/bi992105o","volume":"39","author":"MS Dillingham","year":"2000","unstructured":"Dillingham, M. S., Wigley, D. B. & Webb, M. R. Demonstration of unidirectional single-stranded DNA translocation by PcrA helicase: measurement of step size and translocation speed. Biochem. 39, 205\u2013212 (2000).","journal-title":"Biochem."},{"key":"734_CR37","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/nrm2394","volume":"9","author":"TM Lohman","year":"2008","unstructured":"Lohman, T. M., Tomko, E. J. & Wu, C. G. Non-hexameric DNA helicases and translocases: mechanisms and regulation. Nat. Rev. Mol. Cell Bio. 9, 391\u2013401 (2008).","journal-title":"Nat. Rev. Mol. Cell Bio."},{"key":"734_CR38","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.molcel.2007.03.024","volume":"26","author":"EJ Tomko","year":"2007","unstructured":"Tomko, E. J., Fischer, C. J., Niedziela-Majka, A. & Lohman, T. M. A nonuniform stepping mechanism for E. coli UvrD monomer translocation along single-stranded DNA. Mol. Cell 26, 335\u2013347 (2007).","journal-title":"Mol. Cell"},{"key":"734_CR39","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0092-8674(00)80716-3","volume":"97","author":"SS Velankar","year":"1999","unstructured":"Velankar, S. S., Soultanas, P., Dillingham, M. S., Subramanya, H. S. & Wigley, D. B. Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism. Cell 97, 75\u201384 (1999).","journal-title":"Cell"},{"key":"734_CR40","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1073\/pnas.76.4.1658","volume":"76","author":"GT Yarranton","year":"1979","unstructured":"Yarranton, G. T. & Gefter, M. L. Enzyme-catalyzed DNA unwinding: etudies on Escherichia coli rep protein. Proc. Natl Acad. Sci. USA 76, 1658\u20131662 (1979).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"734_CR41","doi-asserted-by":"publisher","first-page":"5108","DOI":"10.1073\/pnas.0508200103","volume":"103","author":"E Minskaia","year":"2006","unstructured":"Minskaia, E. et al. Discovery of an RNA virus 3\u2032\u2009\u2192\u20095\u2032 exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc. Natl Acad. Sci. USA 103, 5108\u20135113 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"734_CR42","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.virusres.2006.01.017","volume":"117","author":"AE Gorbalenya","year":"2006","unstructured":"Gorbalenya, A. E., Enjuanes, L., Ziebuhr, J. & Snijder, E. J. Nidovirales: evolving the largest RNA virus genome. Virus Res. 117, 17\u201337 (2006).","journal-title":"Virus Res."},{"key":"734_CR43","doi-asserted-by":"publisher","first-page":"270","DOI":"10.4161\/rna.8.2.15013","volume":"8","author":"MR Denison","year":"2011","unstructured":"Denison, M. R., Graham, R. L., Donaldson, E. F., Eckerle, L. D. & Baric, R. S. Coronaviruses: an RNA proofreading machine regulates replication fidelity and diversity. RNA Biol. 8, 270\u2013279 (2011).","journal-title":"RNA Biol."},{"key":"734_CR44","doi-asserted-by":"publisher","first-page":"e00221","DOI":"10.1128\/mBio.00221-18","volume":"9","author":"ML Agostini","year":"2018","unstructured":"Agostini, M. L. et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio. 9, e00221\u201318 (2018).","journal-title":"MBio."},{"key":"734_CR45","doi-asserted-by":"publisher","first-page":"e01456","DOI":"10.7554\/eLife.01456","volume":"2","author":"A Morin","year":"2013","unstructured":"Morin, A. et al. Collaboration gets the most out of software. eLife 2, e01456 (2013).","journal-title":"eLife"},{"key":"734_CR46","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jsb.2005.03.010","volume":"151","author":"C Suloway","year":"2005","unstructured":"Suloway, C. et al. Automated molecular microscopy: the new Leginon system. J. Struct. Biol. 151, 41\u201360 (2005).","journal-title":"J. Struct. Biol."},{"key":"734_CR47","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nmeth.4193","volume":"14","author":"SQ Zheng","year":"2017","unstructured":"Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331\u2013332 (2017).","journal-title":"Nat. Methods"},{"key":"734_CR48","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nmeth.4169","volume":"14","author":"A Punjani","year":"2017","unstructured":"Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290\u2013296 (2017).","journal-title":"Nat. Methods"},{"key":"734_CR49","doi-asserted-by":"crossref","unstructured":"Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).","DOI":"10.7554\/eLife.42166"},{"key":"734_CR50","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1038\/s41592-020-00990-8","volume":"17","author":"A Punjani","year":"2020","unstructured":"Punjani, A., Zhang, H. & Fleet, D. J. Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction. Nat. Methods 17, 1214\u20131221 (2020).","journal-title":"Nat. Methods"},{"key":"734_CR51","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1107\/S2059798318009324","volume":"74","author":"PV Afonine","year":"2018","unstructured":"Afonine, P. V. et al. New tools for the analysis and validation of cryo-EM maps and atomic models. Acta Crystallogr. Sect. D., Struct. Biol. 74, 814\u2013840 (2018).","journal-title":"Acta Crystallogr. Sect. D., Struct. Biol."},{"key":"734_CR52","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr., Sect. D: Biol. Crystallogr. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."},{"key":"734_CR53","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2013a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612 (2004).","journal-title":"J. Comput. Chem."},{"key":"734_CR54","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr., Sect. D: Biol. Crystallogr. 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."},{"key":"734_CR55","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1021\/acs.jctc.9b00251","volume":"16","author":"S Piana","year":"2020","unstructured":"Piana, S., Robustelli, P., Tan, D., Chen, S. & Shaw, D. E. Development of a force field for the simulation of single-chain proteins and protein\u2013protein complexes. J. Chem. Theory Comput. 16, 2494\u20132507 (2020).","journal-title":"J. Chem. Theory Comput."},{"key":"734_CR56","doi-asserted-by":"publisher","first-page":"201713027","DOI":"10.1073\/pnas.1713027115","volume":"115","author":"D Tan","year":"2018","unstructured":"Tan, D., Piana, S., Dirks, R. M. & Shaw, D. E. RNA force field with accuracy comparable to state-of-the-art protein force fields. Proc. Natl Acad. Sci. USA 115, 201713027 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"734_CR57","doi-asserted-by":"publisher","first-page":"5113","DOI":"10.1021\/jp508971m","volume":"119","author":"S Piana","year":"2015","unstructured":"Piana, S., Donchev, A. G., Robustelli, P. & Shaw, D. E. Water dispersion interactions strongly influence simulated structural properties of disordered protein states. J. Phys. Chem. B. 119, 5113\u20135123 (2015).","journal-title":"J. Phys. Chem. B."},{"key":"734_CR58","doi-asserted-by":"crossref","unstructured":"Bowers, K. J. et al. Scalable algorithms for molecular dynamics simulations on commodity clusters. In Proc. ACM\/IEEE Conference on Supercomputing 2006, 11\u201317 November, Tampa, FL, USA 43\u201343 (IEEE, 2006).","DOI":"10.1145\/1188455.1188544"},{"key":"734_CR59","unstructured":"Shaw, D. E. et al. Anton 2: raising the bar for performance and programmability in a special-purpose molecular dynamics supercomputer. in Proc. International Conference for High Performance Computing, Networking, Storage and Analysis, 16\u201321 November, New Orleans, LA, USA 41\u201353 (IEEE, 2014)."},{"key":"734_CR60","doi-asserted-by":"publisher","first-page":"164106","DOI":"10.1063\/1.4825247","volume":"139","author":"RA Lippert","year":"2013","unstructured":"Lippert, R. A. et al. Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure. J. Chem. Phys. 139, 164106 (2013).","journal-title":"J. Chem. Phys."},{"key":"734_CR61","doi-asserted-by":"publisher","first-page":"4177","DOI":"10.1063\/1.467468","volume":"101","author":"GJ Martyna","year":"1994","unstructured":"Martyna, G. J., Tobias, D. J. & Klein, M. L. Constant pressure molecular dynamics algorithms. J. Chem. Phys. 101, 4177\u20134189 (1994).","journal-title":"J. Chem. Phys."},{"key":"734_CR62","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1063\/1.463137","volume":"97","author":"M Tuckerman","year":"1992","unstructured":"Tuckerman, M., Berne, B. J. & Martyna, G. J. Reversible multiple time scale molecular dynamics. J. Chem. Phys. 97, 1990\u20132001 (1992).","journal-title":"J. Chem. Phys."},{"key":"734_CR63","doi-asserted-by":"publisher","first-page":"084113","DOI":"10.1063\/1.5129393","volume":"152","author":"C Predescu","year":"2020","unstructured":"Predescu, C. et al. The u-series: a separable decomposition for electrostatics computation with improved accuracy. J. Chem. Phys. 152, 084113 (2020).","journal-title":"J. Chem. Phys."},{"key":"734_CR64","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nmeth.4347","volume":"14","author":"YZ Tan","year":"2017","unstructured":"Tan, Y. Z. et al. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nat. Methods 14, 793\u2013796 (2017).","journal-title":"Nat. Methods"},{"key":"734_CR65","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr., Sect. D: Biol. Crystallogr. 66, 12\u201321 (2010).","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."}],"container-title":["Nature Structural &amp; Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00734-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00734-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00734-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T01:11:23Z","timestamp":1666660283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00734-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":65,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["734"],"URL":"https:\/\/doi.org\/10.1038\/s41594-022-00734-6","relation":{},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"5 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}