{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:00:42Z","timestamp":1760853642044},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Owing to the size and complexity of large multi-component biological assemblies, the most tractable approach to determining their atomic structure is often to fit high-resolution radiographic or nuclear magnetic resonance structures of isolated components into lower resolution electron density maps of the larger assembly obtained using cryo-electron microscopy (cryo-EM). This hybrid approach to structure determination requires that an atomic resolution structure of each component, or a suitable homolog, is available. If neither is available, then the amount of structural information regarding that component is limited by the resolution of the cryo-EM map. However, even if a suitable homolog cannot be identified using sequence analysis, a search for structural homologs should still be performed because structural homology often persists throughout evolution even when sequence homology is undetectable, As macromolecules can often be described as a collection of independently folded domains, one way of searching for structural homologs would be to systematically fit representative domain structures from a protein domain database into the medium\/low resolution cryo-EM map and return the best fits. Taken together, the best fitting non-overlapping structures would constitute a \u2018mosaic\u2019 backbone model of the assembly that could aid map interpretation and illuminate biological function.<\/jats:p>\n               <jats:p>Result: Using the computational principles of the Scale-Invariant Feature Transform (SIFT), we have developed FOLD-EM\u2014a computational tool that can identify folded macromolecular domains in medium to low resolution (4\u201315 \u00c5) electron density maps and return a model of the constituent polypeptides in a fully automated fashion. As a by-product, FOLD-EM can also do flexible multi-domain fitting that may provide insight into conformational changes that occur in macromolecular assemblies.<\/jats:p>\n               <jats:p>Availability and implementation: FOLD-EM is available at: http:\/\/cs.stanford.edu\/~mitul\/foldEM\/, as a free open source software to the structural biology scientific community.<\/jats:p>\n               <jats:p>Contact: \u00a0mitul@cs.stanford.edu or mcmorais@utmb.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts616","type":"journal-article","created":{"date-parts":[[2012,11,7]],"date-time":"2012-11-07T07:34:13Z","timestamp":1352273653000},"page":"3265-3273","source":"Crossref","is-referenced-by-count":18,"title":["FOLD-EM: automated fold recognition in medium- and low-resolution (4\u201315 \u00c5) electron density maps"],"prefix":"10.1093","volume":"28","author":[{"given":"Mitul","family":"Saha","sequence":"first","affiliation":[{"name":"1 Department of Biochemistry and Molecular Biology and 2Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 7555-0647, USA"},{"name":"1 Department of Biochemistry and Molecular Biology and 2Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 7555-0647, USA"}]},{"given":"Marc C.","family":"Morais","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry and Molecular Biology and 2Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 7555-0647, USA"},{"name":"1 Department of Biochemistry and Molecular Biology and 2Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 7555-0647, USA"}]}],"member":"286","published-online":{"date-parts":[[2012,11,6]]},"reference":[{"key":"2023012513245992100_bts616-B1","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1529\/biophysj.107.122218","article-title":"Normal-mode flexible fitting of high-resolution structure of biological molecules toward one-dimensional low-resolution data","volume":"94","author":"Gorba","year":"2008","journal-title":"Biophys. J."},{"key":"2023012513245992100_bts616-B2","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":"2023012513245992100_bts616-B3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nsb891","article-title":"Coat protein fold and maturation transition of bacteriophage P22 seen at subnanometer resolutions","volume":"10","author":"Jiang","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"2023012513245992100_bts616-B4","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.jsb.2009.12.014","article-title":"An automated procedure for detecting protein folds from sub-nanometer resolution electron density","volume":"170","author":"Khayat","year":"2010","journal-title":"J. Struct. Biol."},{"key":"2023012513245992100_bts616-B5","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/11557067_35","article-title":"Discovery of protein substructures in EM maps","volume":"3692","author":"Lasker","year":"2005","journal-title":"Algorithms in Bioinformatics"},{"key":"2023012513245992100_bts616-B6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1109\/TCBB.2007.1003","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. Comp. Biol. Bioinform."},{"key":"2023012513245992100_bts616-B8","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":"Int. J. Comput. Vis."},{"key":"2023012513245992100_bts616-B9","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1006\/jsbi.1999.4174","article-title":"EMAN: semi-automated software for high-resolution single-particle reconstructions","volume":"128","author":"Ludtke","year":"1999","journal-title":"J. Struct. Biol."},{"key":"2023012513245992100_bts616-B10","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":"2023012513245992100_bts616-B11","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":"16","author":"Ludtke","year":"2008","journal-title":"Structure"},{"key":"2023012513245992100_bts616-B12","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 \u044429","volume":"18","author":"Morais","year":"2005","journal-title":"Mol. Cell"},{"key":"2023012513245992100_bts616-B13","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.str.2003.08.012","article-title":"The atomic structure of RDV reveals the self-assembly mechanism of component proteins","volume":"11","author":"Nakagawa","year":"2003","journal-title":"Structure"},{"key":"2023012513245992100_bts616-B14","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.jmb.2010.08.044","article-title":"The solution structure of the C-terminal Ig-like domain of the bacteriophage \u03bb tail tube protein","volume":"403","author":"Pell","year":"2010","journal-title":"J. Mol. Biol."},{"key":"2023012513245992100_bts616-B15","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":"2023012513245992100_bts616-B16","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.molcel.2008.03.004","article-title":"Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases","volume":"30","author":"Rabl","year":"2008","journal-title":"Mol. Cell"},{"key":"2023012513245992100_bts616-B17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S0076-6879(04)83004-0","article-title":"Protein structure prediction using Rosetta","volume":"383","author":"Rohl","year":"2004","journal-title":"Enzymology"},{"key":"2023012513245992100_bts616-B18","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/bioinformatics\/btq195","article-title":"MOTIF-EM: an automated computational tool for identifying conserved regions in cryoEM structures","volume":"26","author":"Saha","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012513245992100_bts616-B19","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.str.2007.09.021","article-title":"Combining efficient conformational sampling with a deformable elastic network model facilitates structure refinement at low resolution","volume":"15","author":"Schr\u00f6der","year":"2007","journal-title":"Structure"},{"key":"2023012513245992100_bts616-B20","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1107\/S090744490602244X","article-title":"NORMA: a tool for flexible fitting of high-resolution protein structures into low-resolution electron-microscopy-derived density maps","volume":"62","author":"Suhre","year":"2006","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"2023012513245992100_bts616-B21","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":"2023012513245992100_bts616-B29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.str.2007.11.016","article-title":"Protein structure fitting and refinement guided by cryo-EM density","volume":"16","author":"Topf","year":"2008","journal-title":"Structure"},{"key":"2023012513245992100_bts616-B22","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.str.2008.03.005","article-title":"Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics","volume":"16","author":"Trabuco","year":"2008","journal-title":"Structure"},{"key":"2023012513245992100_bts616-B23","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1107\/S0021889897006766","article-title":"MOLREP: an automated program for molecular replacement","volume":"30","author":"Vagin","year":"1997","journal-title":"J. Appl. Cryst."},{"key":"2023012513245992100_bts616-B24","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":"2023012513245992100_bts616-B25","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.jmb.2004.11.005","article-title":"SPI-EM: towards a tool for predicting CATH superfamilies in 3D-EM maps","volume":"345","author":"Vel\u00e1zquez-Muriel","year":"2005","journal-title":"J. Mol. Biol."},{"key":"2023012513245992100_bts616-B26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0076-6879(03)74010-5","article-title":"Docking of atomic models into reconstructions from electron microscopy","volume":"374","author":"Volkmann","year":"2003","journal-title":"Methods Enzymol."},{"key":"2023012513245992100_bts616-B27","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":"2023012513245992100_bts616-B28","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nsb1001-868","article-title":"Electron cryomicroscopy and bioinformatics suggest protein fold models for rice dwarf virus","volume":"8","author":"Zhou","year":"2001","journal-title":"Nat. Struct. Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/24\/3265\/48880135\/bioinformatics_28_24_3265.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/24\/3265\/48880135\/bioinformatics_28_24_3265.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T19:22:17Z","timestamp":1674674537000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/24\/3265\/247356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,6]]},"references-count":28,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2012,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts616","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,12]]},"published":{"date-parts":[[2012,11,6]]}}}