{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:13:37Z","timestamp":1768623217965,"version":"3.49.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T00:00:00Z","timestamp":1276128000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000806","type":"journal-article","created":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T20:30:34Z","timestamp":1276201834000},"page":"e1000806","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":86,"title":["Functional Rotation of the Transporter AcrB: Insights into Drug Extrusion from Simulations"],"prefix":"10.1371","volume":"6","author":[{"given":"Robert","family":"Schulz","sequence":"first","affiliation":[]},{"given":"Attilio V.","family":"Vargiu","sequence":"additional","affiliation":[]},{"given":"Francesca","family":"Collu","sequence":"additional","affiliation":[]},{"given":"Ulrich","family":"Kleinekath\u00f6fer","sequence":"additional","affiliation":[]},{"given":"Paolo","family":"Ruggerone","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2010,6,10]]},"reference":[{"key":"ref1","first-page":"48","article-title":"Efflux as a mechanism of resistance to antimicrobials in Pseudomonas aeruginosa and related bacteria: unanswered questions.","volume":"2","author":"HP Schweizer","year":"2003","journal-title":"Genet Mol Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrmicro1464","article-title":"Multidrug-resistance efflux pumps - not just for resistance.","volume":"4","author":"LJV Piddock","year":"2006","journal-title":"Nat Rev Microbiol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.cell.2007.03.004","article-title":"Molecular mechanisms of antibacterial multidrug resistance.","volume":"128","author":"MN Alekshun","year":"2007","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nature05630","article-title":"Multiple molecular mechanisms for multidrug resistance transporters.","volume":"446","author":"CF Higgins","year":"2007","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/jac\/dki171","article-title":"Efflux-mediated antimicrobial resistance.","volume":"56","author":"K Poole","year":"2005","journal-title":"J Antimicrob Chemother"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrd2200","article-title":"Waltzing transporters and \u2018the dance macabre\u2019 between humans and bacteria.","volume":"6","author":"O Lomovskaya","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref7","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511811098","article-title":"Membrane Structural Biology","author":"M Luckey","year":"2008"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.sbi.2009.02.011","article-title":"Molecular dynamics simulations of membrane channels and transporters.","volume":"19","author":"F Khalili-Araghi","year":"2009","journal-title":"Curr Opin Struct Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.bbapap.2008.10.004","article-title":"Mechanisms of RND multidrug efflux pumps.","volume":"1794","author":"H Nikaido","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1080\/09687680802552257","article-title":"The structure of the efflux pump AcrB in complex with bile acid.","volume":"25","author":"D Drew","year":"2008","journal-title":"Mol Membr Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1128\/jb.178.20.5853-5859.1996","article-title":"Multidrug efflux pumps of Gram-negative bacteria.","volume":"178","author":"H Nikaido","year":"1996","journal-title":"J Bacteriol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"750","DOI":"10.2174\/138945008785747824","article-title":"Membrane permeability and regulation of drug influx and efflux in Enterobacterial pathogens.","volume":"9","author":"A Davin-Regli","year":"2008","journal-title":"Curr Drug Targets"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"8533","DOI":"10.1128\/JB.186.24.8533-8536.2004","article-title":"Interaction between the TolC and AcrA proteins of a multidrug efflux system of Escherichia coli.","volume":"186","author":"F Husain","year":"2004","journal-title":"J Bacteriol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/j.1365-2958.2004.04158.x","article-title":"Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system.","volume":"53","author":"T Touz\u00e9","year":"2004","journal-title":"Mol Microbiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"32116","DOI":"10.1074\/jbc.M402230200","article-title":"AcrA, AcrB, and TolC of Escherichia coli form a stable intermembrane multidrug efflux complex.","volume":"279","author":"EB Tikhonova","year":"2004","journal-title":"J Biol Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"6118","DOI":"10.1128\/JB.00718-07","article-title":"Assembly of the MexAB-OprM multidrug pump of Pseudomonas aeruginosa: component interactions defined by the study of pump mutant suppressors.","volume":"189","author":"D Nehme","year":"2007","journal-title":"J Bacteriol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.bbapap.2008.10.010","article-title":"Structural and functional diversity of bacterial membrane fusion proteins.","volume":"1794","author":"HI Zgurskaya","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"719","DOI":"10.2174\/138945008785747743","article-title":"Structure and mechanism of drug efflux machinery in Gram-negative bacteria.","volume":"9","author":"Z Pietras","year":"2008","journal-title":"Curr Drug Targets"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.bbapap.2009.02.017","article-title":"Assembly and transport mechanism of tripartite drug efflux systems.","volume":"1794","author":"R Misra","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1111\/j.1365-2958.1994.tb00362.x","article-title":"Two novel families of bacterial membrane proteins concerned with nodulation, cell division and transport.","volume":"11","author":"MH Saier","year":"1994","journal-title":"Mol Microbiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"9051","DOI":"10.1073\/pnas.0902400106","article-title":"A coordinated network of transporters with overlapping specificities provides a robust survival strategy.","volume":"106","author":"N Tal","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1128\/AAC.49.5.1865-1871.2005","article-title":"A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline.","volume":"49","author":"F McAleese","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/35016007","article-title":"Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export.","volume":"405","author":"V Koronakis","year":"2000","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.str.2005.11.015","article-title":"Conformational flexibility in the multidrug efflux system protein AcrA.","volume":"14","author":"J Mikolosko","year":"2006","journal-title":"Structure"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"7173","DOI":"10.1073\/pnas.0900693106","article-title":"The assembled structure of a complete tripartite bacterial multidrug efflux pump.","volume":"106","author":"M Symmons","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S1369-5274(98)80083-0","article-title":"Multiple antibiotic resistance and efflux.","volume":"1","author":"H Nikaido","year":"1998","journal-title":"Curr Opin Microbiol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nature01050","article-title":"Crystal structure of bacterial multidrug efflux transporter AcrB.","volume":"419","author":"S Murakami","year":"2002","journal-title":"Nature"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2174\/138945008785747789","article-title":"The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance.","volume":"9","author":"MA Seeger","year":"2008","journal-title":"Curr Drug Targets"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.sbi.2008.06.007","article-title":"Multidrug efflux transporter, AcrB\u2013the pumping mechanism.","volume":"18","author":"S Murakami","year":"2008","journal-title":"Curr Opin Struct Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature05076","article-title":"Crystal structures of a multidrug transporter reveal a functionally rotating mechanism.","volume":"443","author":"S Murakami","year":"2006","journal-title":"Nature"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1126\/science.1131542","article-title":"Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism.","volume":"313","author":"MA Seeger","year":"2006","journal-title":"Science"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1371\/journal.pbio.0050007","article-title":"Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors.","volume":"5","author":"G Sennhauser","year":"2007","journal-title":"PLoS Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nsmb.1379","article-title":"Engineered disulfide bonds support the functional rotation mechanism of multidrug efflux pump AcrB.","volume":"15","author":"MA Seeger","year":"2008","journal-title":"Nat Struct Mol Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1128\/JB.01441-08","article-title":"Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism.","volume":"191","author":"Y Takatsuka","year":"2009","journal-title":"J Bacteriol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"8225","DOI":"10.1128\/JB.00912-08","article-title":"Site-directed mutagenesis reveals putative substrate binding residues in the Escherichia coli RND efflux pump AcrB.","volume":"190","author":"JA Bohnert","year":"2008","journal-title":"J Bacteriol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.1529\/biophysj.108.136028","article-title":"Gating at both ends and breathing in the middle: Conformational dynamics of TolC.","volume":"95","author":"L Vaccaro","year":"2008","journal-title":"Biophys J"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1016\/j.bpj.2009.01.021","article-title":"Transitions between closed and open conformations of TolC: The effects of ions in simulations.","volume":"96","author":"R Schulz","year":"2009","journal-title":"Biophys J"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1529\/biophysj.105.080010","article-title":"Flexibility in a drug transport accessory protein: molecular dynamics simulations of MexA.","volume":"91","author":"L Vaccaro","year":"2006","journal-title":"Biophys J"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/08927029308022170","article-title":"Targeted molecular-dynamics simulation of conformational change - application to the T\u2013R transition in insulin.","volume":"10","author":"J Schlitter","year":"1993","journal-title":"Mol Simul"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0969-2126(02)00789-X","article-title":"A dynamic analysis of the rotation mechanism for conformational change in F<sub>1<\/sub>-ATPase.","volume":"10","author":"J Ma","year":"2002","journal-title":"Structure"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/prot.21374","article-title":"Targeted molecular dynamics simulation studies of binding and conformational changes in E. coli MurD.","volume":"68","author":"A Perdih","year":"2007","journal-title":"Proteins"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1021\/ct9000153","article-title":"Comparison of three perturbation molecular dynamics methods for modeling conformational transitions.","volume":"5","author":"H Huang","year":"2009","journal-title":"J Chem Theor Comp"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"5854","DOI":"10.1073\/pnas.0901695106","article-title":"Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli.","volume":"106","author":"K Nagano","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1515\/BC.2009.090","article-title":"Structural and functional aspects of the multidrug efflux pump AcrB.","volume":"390","author":"T Eicher","year":"2009","journal-title":"Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1080\/07391102.1999.10508297","article-title":"A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat.","volume":"16","author":"T Cheatham","year":"1999","journal-title":"J Biomol Struct Dyn"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water.","volume":"79","author":"WL Jorgensen","year":"1983","journal-title":"J Chem Phys"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"8021","DOI":"10.1021\/j100384a009","article-title":"Ion-water interaction potentials derived from free energy perturbation simulations.","volume":"94","author":"J Aaqvist","year":"1990","journal-title":"J Phys Chem"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general amber force field.","volume":"25","author":"J Wang","year":"2004","journal-title":"J Comp Chem"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0010-4655(95)00041-D","article-title":"Amber, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculationsto simulate the structural and energetic properties of molecules.","volume":"91","author":"DA Pearlman","year":"1995","journal-title":"Comp Phys Commun"},{"key":"ref50","article-title":"Gaussian 03, Revision C.02","author":"MJ Frisch","year":"2004"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1002\/jcc.20748","article-title":"Performance of the general amber force field in modeling aqueous POPC membrane bilayers.","volume":"28","author":"B J\u00f3j\u00e1rt","year":"2007","journal-title":"J Comput Chem"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD.","volume":"26","author":"JC Phillips","year":"2005","journal-title":"J Comput Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1006\/jmbi.2000.4014","article-title":"A dynamic model for the allosteric mechanism of GroEL.","volume":"302","author":"J Ma","year":"2000","journal-title":"J Mol Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD \u2013 Visual Molecular Dynamics.","volume":"14","author":"WF Humphrey","year":"1996","journal-title":"J Mol Graph"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000806","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T14:55:13Z","timestamp":1589036113000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000806"}},"subtitle":[],"editor":[{"given":"Emad","family":"Tajkhorshid","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2010,6,10]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2010,6,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000806","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,10]]}}}