{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:13:51Z","timestamp":1760955231770},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2315,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We present a new, first-of-its-kind, fully automated computational tool MOTIF-EM for identifying regions or domains or motifs in cryoEM maps of large macromolecular assemblies (such as chaperonins, viruses, etc.) that remain conformationally conserved. As a by-product, regions in structures that are not conserved are revealed: this can indicate local molecular flexibility related to biological activity. MOTIF-EM takes cryoEM volumetric maps as inputs. The technique used by MOTIF-EM to detect conserved sub-structures is inspired by a recent breakthrough in 2D object recognition. The technique works by constructing rotationally invariant, low-dimensional representations of local regions in the input cryoEM maps. Correspondences are established between the reduced representations (by comparing them using a simple metric) across the input maps. The correspondences are clustered using hash tables and graph theory is used to retrieve conserved structural domains or motifs. MOTIF-EM has been used to extract conserved domains occurring in large macromolecular assembly maps, including as those of viruses P22 and epsilon 15, Ribosome 70S, GroEL, that remain structurally conserved in different functional states. Our method can also been used to build atomic models for some maps. We also used MOTIF-EM to identify the conserved folds shared among dsDNA bacteriophages HK97, Epsilon 15, and \u00f429, though they have low-sequence similarity.<\/jats:p>\n               <jats:p>Contact: \u00a0mitul@cs.stanford.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq195","type":"journal-article","created":{"date-parts":[[2010,6,7]],"date-time":"2010-06-07T07:28:13Z","timestamp":1275895693000},"page":"i301-i309","source":"Crossref","is-referenced-by-count":8,"title":["MOTIF-EM: an automated computational tool for identifying conserved regions in CryoEM structures"],"prefix":"10.1093","volume":"26","author":[{"given":"Mitul","family":"Saha","sequence":"first","affiliation":[{"name":"1 NIH Center for Biomedical Computation, Stanford University, Stanford, CA 94305, 2 Department of Structural Biology, Stanford School of Medicine, Stanford, CA 94305 and 3 National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX 77030, USA"}]},{"given":"Michael","family":"Levitt","sequence":"additional","affiliation":[{"name":"1 NIH Center for Biomedical Computation, Stanford University, Stanford, CA 94305, 2 Department of Structural Biology, Stanford School of Medicine, Stanford, CA 94305 and 3 National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX 77030, USA"}]},{"given":"Wah","family":"Chiu","sequence":"additional","affiliation":[{"name":"1 NIH Center for Biomedical Computation, Stanford University, Stanford, CA 94305, 2 Department of Structural Biology, Stanford School of Medicine, Stanford, CA 94305 and 3 National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX 77030, USA"}]}],"member":"286","published-online":{"date-parts":[[2010,6,1]]},"reference":[{"key":"2023012508061914200_B1","article-title":"On the relative efficiency of maximal clique enumeration algorithms, with applications to high-throughput computational biology","volume-title":"Proceedings of International Conference on Research Trends in Science and Technology","author":"Abu-Khzam","year":"2005"},{"key":"2023012508061914200_B2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.str.2006.11.008","article-title":"Identification of secondary structure elements in intermediate resolution density maps","volume":"15","author":"Baker","year":"2007","journal-title":"Structure"},{"key":"2023012508061914200_B3","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jmb.2004.02.066","article-title":"Fast fitting of atomic structures to low-resolution electron density maps by surface overlap maximization","volume":"338","author":"Ceulemans","year":"2004","journal-title":"J. Mol. Biol."},{"key":"2023012508061914200_B4","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.tcb.2006.01.002","article-title":"Structural biology of cellular machines","volume":"16","author":"Chiu","year":"2006","journal-title":"Trends Cell Biol."},{"key":"2023012508061914200_B5","volume-title":"Introduction to Robotics.","author":"Craig","year":"2005","edition":"3rd"},{"key":"2023012508061914200_B6","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1364\/JOSAA.4.000629","article-title":"Closed-form solution of absolute orientation using unit quaternions","volume":"4","author":"Horn","year":"1987","journal-title":"J. Optical Soc. Amer. A"},{"key":"2023012508061914200_B7","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.sbi.2005.08.004","article-title":"Electron cryomicroscopy of single particles at subnanometer resolution","volume":"15","author":"Jiang","year":"2005","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2023012508061914200_B8","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1006\/jmbi.2001.4633","article-title":"Bridging the information gap: computational tools for intermediate resolution structure interpretation","volume":"208","author":"Jiang","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2023012508061914200_B9","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/nature04487","article-title":"Structure of epsilon15 phage reveals organization of genome and DNA packaging\/injection apparatus","volume":"439","author":"Jiang","year":"2006","journal-title":"Nature"},{"key":"2023012508061914200_B10","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/nature06665","article-title":"Backbone structure of the infectious \u03b5 15 virus capsid revealed by electron cryomicroscopy","volume":"451","author":"Jiang","year":"2008","journal-title":"Nature"},{"key":"2023012508061914200_B11","first-page":"423","article-title":"Discovery of protein substructures in EM maps","author":"Lasker","year":"2005","journal-title":"WABI"},{"key":"2023012508061914200_B12","first-page":"28","article-title":"EMatch: discovery of high resolution structural homologues of protein domains in intermediate resolution Cryo-EM maps","volume":"4","author":"Lasker","year":"2007","journal-title":"IEEE Trans. CBB"},{"key":"2023012508061914200_B13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1023\/B:VISI.0000029664.99615.94","article-title":"Distinctive image features from scale-invariant keypoints","volume":"60","author":"Lowe","year":"2004","journal-title":"IJCV"},{"key":"2023012508061914200_B14","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.str.2004.05.006","article-title":"Seeing GroEL at 6 \u00c5 resolution by single particle electron cryomicroscopy","volume":"12","author":"Ludtke","year":"2004","journal-title":"Structure"},{"key":"2023012508061914200_B15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1006\/jsbi.1999.4174","article-title":"EMAN: semiautomated software for high-resolution single-particle reconstructions","volume":"128","author":"Ludtke","year":"1999","journal-title":"J. Struct. Biol."},{"key":"2023012508061914200_B16","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.str.2008.02.007","article-title":"De novo backbone trace of GroEL from single particle electron cryomicroscopy","volume":"6","author":"Ludtke","year":"2008","journal-title":"Structure"},{"key":"2023012508061914200_B17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.molcel.2005.03.013","article-title":"Conservation of the capsid structure in tailed dsDNA bacteriophages: the psuedoatomic structure of \u00f429","volume":"18","author":"Morais","year":"2005","journal-title":"Mol. Cell"},{"key":"2023012508061914200_B18","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comp. Chem."},{"key":"2023012508061914200_B19","first-page":"1332","article-title":"Docking structures of domains into maps from cryo-electron microscopy using local correlation","volume":"D56","author":"Roseman","year":"2000","journal-title":"Acta Crystallogr."},{"key":"2023012508061914200_B20","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1006\/jsbi.2002.4435","article-title":"Combining electron microscopic with X-ray crystallographic structures","volume":"136","author":"Rossmann","year":"2001","journal-title":"J. Struct. Biol."},{"key":"2023012508061914200_B21","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jsb.2004.03.002","article-title":"Normal node based flexible fitting of high-resolution structure into low-resolution experimental data from Cryo-EM","volume":"147","author":"Tama","year":"2004","journal-title":"J. Struct Biol."},{"key":"2023012508061914200_B22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jsb.2004.11.004","article-title":"Structural characterization of components of protein assemblies by comparative modeling and electron cryo-microscopy","volume":"149","author":"Topf","year":"2005","journal-title":"J. Struct. Biol."},{"key":"2023012508061914200_B23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0092-8674(03)00476-8","article-title":"Locking and unlocking of ribosomal motions","volume":"114","author":"Valle","year":"2003","journal-title":"Cell"},{"key":"2023012508061914200_B24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0076-6879(03)74010-5","article-title":"Docking of atomic models into reconstruction from electron microscopy","volume":"374","author":"Volkmann","year":"2003","journal-title":"Methods Enzymol."},{"key":"2023012508061914200_B25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1006\/jsbi.2000.4350","article-title":"Using situs for flexible and rigid-body fitting of multiresolution single-molecule data","volume":"133","author":"Wriggers","year":"2001","journal-title":"J. Struct. Biol."},{"key":"2023012508061914200_B26","first-page":"568","article-title":"Computational approaches for automatic structural analysis of large bio-molecular complexes","volume":"5","author":"Yu","year":"2007","journal-title":"IEEE CBB"},{"key":"2023012508061914200_B27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsb.2008.09.006","article-title":"JADAS: a customizable automated data acquisition system and its application to ice-embedded single particles","volume":"165","author":"Zhang","year":"2009","journal-title":"J. Struct. Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/12\/i301\/48859230\/bioinformatics_26_12_i301.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/12\/i301\/48859230\/bioinformatics_26_12_i301.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T08:10:08Z","timestamp":1674634208000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/26\/12\/i301\/283683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,1]]},"references-count":27,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2010,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btq195","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,6,15]]},"published":{"date-parts":[[2010,6,1]]}}}