{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T20:22:19Z","timestamp":1775074939198,"version":"3.50.1"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"2","content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000289","type":"journal-article","created":{"date-parts":[[2009,2,19]],"date-time":"2009-02-19T22:58:27Z","timestamp":1235084307000},"page":"e1000289","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":100,"title":["Conformational Changes and Slow Dynamics through Microsecond Polarized Atomistic Molecular Simulation of an Integral Kv1.2 Ion Channel"],"prefix":"10.1371","volume":"5","author":[{"given":"P\u00e4r","family":"Bjelkmar","sequence":"first","affiliation":[]},{"given":"Perttu S.","family":"Niemel\u00e4","sequence":"additional","affiliation":[]},{"given":"Ilpo","family":"Vattulainen","sequence":"additional","affiliation":[]},{"given":"Erik","family":"Lindahl","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2009,2,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.eplepsyres.2008.03.013","article-title":"Polyunsaturated fatty acids and cerebrospinal fluid from children on the ketogenic diet open a voltage-gated K channel: a putative mechanism of antiseizure action.","volume":"80","author":"X Xu","year":"2008","journal-title":"Epilepsy Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.280.5360.69","article-title":"The structure of the potassium channel: molecular basis of K<sup>+<\/sup> conduction and selectivity.","volume":"280","author":"DA Doyle","year":"1998","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"6900","DOI":"10.1073\/pnas.0800873105","article-title":"Molecular mechanism of pH sension in KcsA potassium channels.","volume":"105","author":"A Thompson","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nature01581","article-title":"The principle of gating charge movement in a voltage-dependent K<sup>+<\/sup> channel.","volume":"423","author":"Y Jiang","year":"2003","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"15441","DOI":"10.1073\/pnas.0507651102","article-title":"Structure of the KvAP voltage-dependent K<sup>+<\/sup> channel and its dependence on the lipid membrane.","volume":"102","author":"SY Lee","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1126\/science.1116269","article-title":"Crystal structure of a mammalian voltage-dependent Shaker family K<sup>+<\/sup> channel.","volume":"309","author":"SB Long","year":"2005","journal-title":"Science"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature06265","article-title":"Atomic structure of a voltage-dependent K<sup>+<\/sup> channel in a lipid membrane-like environment.","volume":"450","author":"SB Long","year":"2007","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/0896-6273(95)90078-0","article-title":"Evidence for voltage-dependent S4 movement in sodium channels.","volume":"15","author":"N Yang","year":"1995","journal-title":"Neuron"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/S0896-6273(00)80143-9","article-title":"Contribution of the S4 segment to gating charge in the Shaker K<sup>+<\/sup> channel.","volume":"16","author":"SK Aggarwal","year":"1996","journal-title":"Neuron"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S0896-6273(00)80142-7","article-title":"Voltage-sensing residues in the S2 and S4 segments of the Shaker K<sup>+<\/sup> channel.","volume":"16","author":"SA Seoh","year":"1996","journal-title":"Neuron"},{"key":"ref11","article-title":"Ionic Channels of Excitable Membranes","author":"B Hille","year":"1992"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"7611","DOI":"10.1073\/pnas.1332409100","article-title":"Fast gating in the Shaker K<sup>+<\/sup> channel and the energy landscape of activation.","volume":"100","author":"D Sigg","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1085\/jgp.200409197","article-title":"The cooperative voltage sensor motion that gates a potassium channel.","volume":"125","author":"M Pathak","year":"2005","journal-title":"J Gen Physiol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S0006-3495(94)80888-4","article-title":"An engineered cysteine in the external mouth of a K<sup>+<\/sup> channel allows inactivation to be modulated by metal binding.","volume":"66","author":"G Yellen","year":"1994","journal-title":"Biophys J"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0896-6273(00)80106-3","article-title":"Dynamic rearrangement of the outer mouth of a k+ channel during gating.","volume":"16","author":"Y Liu","year":"1996","journal-title":"Neuron"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0006-3495(99)77194-8","article-title":"Contribution of the selectivity filter to inactivation in potassium channels.","volume":"76","author":"L Kiss","year":"1999","journal-title":"Biophys J"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/nsmb1309","article-title":"Molecular driving forces determining potassium channel slow inactivation.","volume":"14","author":"JF Cordero-Morales","year":"2007","journal-title":"Nat Struct Mol Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1126\/science.1553560","article-title":"The size of gating charge in wild-type and mutant Shaker potassium channels.","volume":"255","author":"N Schoppa","year":"1992","journal-title":"Science"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1016\/S0006-3495(03)74708-0","article-title":"Electrostatic model of S4 motion in voltage-gated ion channels.","volume":"85","author":"H Lecar","year":"2003","journal-title":"Biophys J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1085\/jgp.20028660","article-title":"Voltage sensor movements.","volume":"120","author":"F Bezanilla","year":"2002","journal-title":"J Gen Physiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1146\/annurev.bi.55.070186.004513","article-title":"Molecular properties of voltage-sensitive sodium channels.","volume":"55","author":"WA Catterall","year":"1986","journal-title":"Annu Rev Biochem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.tins.2004.03.008","article-title":"Stirring up controversy with a voltage sensor paddle.","volume":"27","author":"CA Ahern","year":"2004","journal-title":"Trends Neurosci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev.cellbio.21.020404.145837","article-title":"How does voltage open an ion channel?","volume":"22","author":"F Tombola","year":"2006","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1085\/jgp.117.1.69","article-title":"Electrostatics and the gating pore of shaker potassium channels.","volume":"117","author":"L Islas","year":"2001","journal-title":"J Gen Physiol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nature02270","article-title":"A proton pore in a potassium channel voltage sensor reveals a focused electric field.","volume":"427","author":"DM Starace","year":"2004","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1529\/biophysj.107.112540","article-title":"Dynamics of the Kv1.2 voltage-gated K<sup>+<\/sup> channel in a membrane environment.","volume":"93","author":"V Jogini","year":"2007","journal-title":"Biophys J"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"17600","DOI":"10.1073\/pnas.0807387105","article-title":"S4-based voltage sensors have three major conformations.","volume":"105","author":"CA Villalba-Galea","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"7292","DOI":"10.1073\/pnas.0602350103","article-title":"Voltage sensor conformations in the open and closed states in ROSETTA structural models of K<sup>+<\/sup> channels.","volume":"103","author":"V Yarov-Yarovoy","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"L90","DOI":"10.1529\/biophysj.106.096065","article-title":"A voltage-sensor water pore.","volume":"91","author":"JA Freites","year":"2006","journal-title":"Biophys J"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1529\/biophysj.105.072199","article-title":"The intrinsic flexibility of the Kv voltage sensor and its implications for channel gating.","volume":"90","author":"ZA Sands","year":"2006","journal-title":"Biophys J"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"L64","DOI":"10.1529\/biophysj.106.080754","article-title":"Environment of the gating charges in the Kv1.2 Shaker potassium channel.","volume":"90","author":"W Treptow","year":"2006","journal-title":"Biophys J"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1529\/biophysj.107.115741","article-title":"The last few frames of the voltage-gating movie.","volume":"93","author":"FJ Sigworth","year":"2007","journal-title":"Biophys J"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1021\/jp709675e","article-title":"Gating motions in voltage-gated potassium channels revealed by coarse-grained molecular dynamics simulations.","volume":"112","author":"W Treptow","year":"2008","journal-title":"J Phys Chem B"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1529\/biophysj.108.130658","article-title":"Molecular dynamics simulation of Kv channel voltage sensor helix in a lipid membrane with applied electric field.","volume":"95","author":"M Nishizawa","year":"2008","journal-title":"Biophys J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/ct700301q","article-title":"GROMACS 4.0: algorithms for highly efficient, load-balanced, and scalable molecular simulation.","volume":"4","author":"H Berk","year":"2008","journal-title":"J Chem Theory Comput"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0960-9822(93)90255-M","article-title":"Structural similarity of DNA-binding domains of bacteriophage repressors and the globin core.","volume":"3","author":"S Subbiah","year":"1993","journal-title":"Curr Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: visual molecular dynamics.","volume":"14","author":"W Humphrey","year":"1996","journal-title":"J Mol Graph"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.str.2007.01.004","article-title":"How does a voltage sensor interact with a lipid bilayer? Simulations of a potassium channel domain.","volume":"15","author":"ZA Sands","year":"2007","journal-title":"Structure"},{"key":"ref39","first-page":"331","article-title":"Interaction models for water in relation to protein hydration.","author":"HJC Berendsen","year":"1981"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jp003919d","article-title":"Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides.","volume":"105","author":"GA Kaminski","year":"2001","journal-title":"J Phys Chem B"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/S0006-3495(97)78845-3","article-title":"Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature.","volume":"72","author":"O Berger","year":"1997","journal-title":"Biophys J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1063\/1.1389469","article-title":"Molecular dynamics simulation of NMR relaxation rates and slow dynamics in lipid bilayers.","volume":"115","author":"E Lindahl","year":"2001","journal-title":"J Chem Phys"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1529\/biophysj.104.046821","article-title":"Experimental validation of molecular dynamics simulations of lipid bilayers: a new approach.","volume":"88","author":"R Benz","year":"2005","journal-title":"Biophys J"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: fast, flexible, and free.","volume":"26","author":"D Van Der Spoel","year":"2005","journal-title":"J Comput Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: a linear constraint solver for molecular simulations.","volume":"18","author":"B Hess","year":"1997","journal-title":"J Comput Chem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/jcc.540130805","article-title":"SETTLE: an analytical version of the SHAKE and RATTLE algorithms for rigid water models.","volume":"13","author":"S Miyamoto","year":"1992","journal-title":"J Comput Chem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1021\/ct700200b","article-title":"P-LINCS: a parallel linear constraint solver for molecular simulation.","volume":"4","author":"B Hess","year":"2008","journal-title":"J Chem Theory Comput"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method.","volume":"103","author":"U Essmann","year":"1995","journal-title":"J Chem Phys"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular dynamics with coupling to an external bath.","volume":"81","author":"HJC Berendsen","year":"1984","journal-title":"J Chem Phys"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1529\/biophysj.108.136499","article-title":"The membrane potential and its representation by a constant electric field in computer simulations.","volume":"95","author":"B Roux","year":"2008","journal-title":"Biophys J"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1529\/biophysj.108.129437","article-title":"Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations.","volume":"95","author":"RA B\u00f6ckmann","year":"2008","journal-title":"Biophys J"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1529\/biophysj.104.039628","article-title":"Coupled motions between pore and voltage-sensor domains: a model for Shaker B, a voltage-gated potassium channel.","volume":"87","author":"W Treptow","year":"2004","journal-title":"Biophys J"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1085\/jgp.200809962","article-title":"Atomic constraints between the voltage sensor and the pore domain in a voltage-gated K<sup>+<\/sup> channel of known structure.","volume":"131","author":"A Lewis","year":"2008","journal-title":"J Gen Physiol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1126\/science.1116270","article-title":"Voltage sensor of Kv1.2: structural basis of electromechanical coupling.","volume":"309","author":"SB Long","year":"2005","journal-title":"Science"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0006-3495(97)78797-6","article-title":"Electrostatic interactions between transmembrane segments mediate folding of Shaker K<sup>+<\/sup> channel subunits.","volume":"72","author":"SK Tiwari-Woodruff","year":"1997","journal-title":"Biophys J"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0896-6273(00)80056-2","article-title":"Transmembrane movement of the shaker K<sup>+<\/sup> channel S4.","volume":"16","author":"HP Larsson","year":"1996","journal-title":"Neuron"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"7904","DOI":"10.1073\/pnas.0702638104","article-title":"Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel.","volume":"104","author":"FV Campos","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref58","first-page":"11915","article-title":"Molecular dynamics and monte carlo simulations favor the \u03b1-helical form for alanine-based peptides in water.","volume":"116","author":"J Tirado-Rives","year":"1994","journal-title":"J Am Chem Soc"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"11915","DOI":"10.1021\/ja00105a034","article-title":"3<sub>10<\/sub> helix versus \u03b1-helix: a molecular dynamics study of conformational preferences of aib and alanine.","volume":"116","author":"L Zhang","year":"1994","journal-title":"J Am Chem Soc"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"13280","DOI":"10.1073\/pnas.2233312100","article-title":"Trp-cage: folding free energy landscape in explicit water.","volume":"100","author":"R Zhou","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev.biophys.36.040306.132643","article-title":"Bilayer thickness and membrane protein function: an energetic perspective.","volume":"36","author":"OS Andersen","year":"2007","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1126\/science.1094113","article-title":"Functional conversion between A-type and delayed rectifier K<sup>+<\/sup> channels by membrane lipids.","volume":"304","author":"D Oliver","year":"2004","journal-title":"Science"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1124\/mol.63.6.1417","article-title":"Local anesthetic block of Kv channels: role of the S6 helix and the S5\u2013S6 linker for bupivacaine action.","volume":"63","author":"J Nilsson","year":"2003","journal-title":"Mol Pharmacol"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0896-6273(00)80307-4","article-title":"Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K<sup>+<\/sup> channels.","volume":"18","author":"KJ Swartz","year":"1997","journal-title":"Neuron"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"10771","DOI":"10.1021\/bi026215y","article-title":"Lipids in the structure, folding, and function of the KcsA K<sup>+<\/sup> channel.","volume":"41","author":"FI Valiyaveetil","year":"2002","journal-title":"Biochemistry"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nature05416","article-title":"Phospholipids and the origin of cationic gating charges in voltage sensors.","volume":"444","author":"D Schmidt","year":"2006","journal-title":"Nature"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.neuron.2005.08.020","article-title":"Focused electric field across the voltage sensor of potassium channels.","volume":"48","author":"CA Ahern","year":"2005","journal-title":"Neuron"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"15059","DOI":"10.1073\/pnas.0507618102","article-title":"Interface connections of a transmembrane voltage sensor.","volume":"102","author":"JA Freites","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1529\/biophysj.105.070755","article-title":"The interfacial lipid binding site on the potassium channel KcsA is specific for anionic phospholipids.","volume":"89","author":"P Marius","year":"2005","journal-title":"Biophys J"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1529\/biophysj.105.071407","article-title":"Anionic phospholipid interactions with the potassium channel KcsA: simulation studies.","volume":"90","author":"SS Deol","year":"2006","journal-title":"Biophys J"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bbamem.2004.06.012","article-title":"Lipids in membrane protein structures.","volume":"1666","author":"H Palsdottir","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neuron.2007.09.023","article-title":"Closing in on the resting state of the Shaker K<sup>+<\/sup> channel.","volume":"56","author":"MM Pathak","year":"2007","journal-title":"Neuron"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1085\/jgp.115.3.257","article-title":"Independence and cooperativity in rearrangements of a potassium channel voltage sensor revealed by single subunit fluorescence.","volume":"115","author":"LM Mannuzzu","year":"2000","journal-title":"J Gen Physiol"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1371\/journal.pcbi.0030034","article-title":"Assessing the nature of lipid raft membranes.","volume":"3","author":"PS Niemela","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/bip.360221211","article-title":"Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features.","volume":"22","author":"W Kabsch","year":"1983","journal-title":"Biopolymers"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T20:52:23Z","timestamp":1540327943000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000289"}},"subtitle":[],"editor":[{"given":"Benoit","family":"Roux","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2009,2,20]]},"references-count":75,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,2,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000289","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,20]]}}}