{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:55:45Z","timestamp":1787021745875,"version":"3.56.0"},"reference-count":71,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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.1002761","type":"journal-article","created":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T17:05:29Z","timestamp":1351789529000},"page":"e1002761","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":151,"title":["pH-Dependent Conformational Changes in Proteins and Their Effect on Experimental pKas: The Case of Nitrophorin 4"],"prefix":"10.1371","volume":"8","author":[{"given":"Natali V.","family":"Di Russo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario A.","family":"Estrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo A.","family":"Mart\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian E.","family":"Roitberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/pro.19","article-title":"A summary of the measured pK values of the ionizable groups in folded proteins","volume":"18","author":"GR Grimsley","year":"2009","journal-title":"Protein Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1002\/prot.22621","article-title":"Improving the analysis of NMR spectra tracking pH-induced conformational changes: removing artefacts of the electric field on the NMR chemical shift","volume":"78","author":"P Kuki\u0107","year":"2010","journal-title":"Proteins"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1080\/15216540211468","article-title":"Structural Basis of Perturbed pKa Values of Catalytic Groups in Enzyme Active Sites","volume":"53","author":"TK Harris","year":"2002","journal-title":"IUBMB Life"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.bbabio.2006.06.005","article-title":"Factors influencing the energetics of electron and proton transfers in proteins. What can be learned from calculations","volume":"1757","author":"MR Gunner","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1152\/physiol.00035.2006","article-title":"Intracellular pH sensors: design principles and functional significance","volume":"22","author":"J Srivastava","year":"2007","journal-title":"Physiology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"9958","DOI":"10.1021\/bi9613234","article-title":"The pKa of the general acid\/base carboxyl group of a glycosidase cycles during catalysis: a 13C-NMR study of <italic>Bacillus circulans<\/italic> xylanase","volume":"35","author":"LP McIntosh","year":"1996","journal-title":"Biochemistry"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"14985","DOI":"10.1021\/bi970071j","article-title":"Microscopic pKa values of <italic>Escherichia coli<\/italic> thioredoxin","volume":"36","author":"PT Chivers","year":"1997","journal-title":"Biochemistry"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/S0006-3495(00)76411-3","article-title":"High apparent dielectric constants inthe interior of a protein reflect water penetration","volume":"79","author":"JJ Dwyer","year":"2000","journal-title":"Biophys J"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0022-2836(91)80195-Z","article-title":"In a staphylococcal nuclease mutant the side-chain of a lysine replacing valine 66 is fully buried in the hydrophobic core","volume":"221","author":"WE Stites","year":"1991","journal-title":"J Mol Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/prot.1106","article-title":"What Are the Dielectric \u201cConstants\u201d of Proteins and How To Validate Electrostatic Models?","volume":"44","author":"CN Schutz","year":"2001","journal-title":"Proteins"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"10118","DOI":"10.1021\/bi000766b","article-title":"Kinetics and equilibria in ligand binding by nitrophorins 1\u20134: evidence for stabilization of a nitric oxide-ferriheme complex through a ligand-induced conformational trap","volume":"39","author":"JF Andersen","year":"2000","journal-title":"Biochemistry"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1021\/ja808105d","article-title":"Effect of mutation of carboxyl side-chain amino acids near the heme on the midpoint potentials and ligand binding constants of nitrophorin 2 and its NO, histamine, and imidazole complexes","volume":"131","author":"RE Berry","year":"2009","journal-title":"J Am Chem Soc"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.bbabio.2011.01.004","article-title":"Exploration of the cytochrome c oxidase pathway puzzle and examination of the origin of elusive mutational effects","volume":"1807","author":"S Chakrabarty","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1021\/ja01468a021","article-title":"Ionization-linked Changes in Protein Conformation. I. Theory","volume":"83","author":"C Tanford","year":"1961","journal-title":"J Am Chem Soc"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0065-3233(08)60011-X","article-title":"Heme Proteins","volume":"4","author":"J Wyman","year":"1948","journal-title":"Adv Protein Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1006\/jmbi.1993.1294","article-title":"On the pH dependence of protein stability","volume":"231","author":"A Yang","year":"1993","journal-title":"J Mol Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1006\/jmbi.1994.1301","article-title":"Prediction of pH-dependent properties of proteins","volume":"238","author":"J Antosiewicz","year":"1994","journal-title":"J Mol Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"9556","DOI":"10.1021\/j100176a093","article-title":"Multiple-site titration curves of proteins: an analysis of exact and approximate methods for their calculation","volume":"95","author":"D Bashford","year":"1991","journal-title":"J Phys Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/S0006-3495(02)73940-4","article-title":"Combining conformational flexibility and continuum electrostatics for calculating pK(a)s in proteins","volume":"83","author":"RE Georgescu","year":"2002","journal-title":"Biophys J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/S0006-3495(97)78851-9","article-title":"Incorporating protein conformational flexibility into the calculation of pH-dependent protein properties","volume":"72","author":"EG Alexov","year":"1997","journal-title":"Biophys J"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1529\/biophysj.106.090266","article-title":"High apparent dielectric constant inside a protein reflects structural reorganization coupled to the ionization of an internal Asp","volume":"92","author":"DA Karp","year":"2007","journal-title":"Biophys J"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1073\/pnas.0407499102","article-title":"Local conformational fluctuations can modulate the coupling between proton binding and global structural transitions in proteins","volume":"102","author":"ST Whitten","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S0167-4838(00)00165-5","article-title":"Nitrophorins and related antihemostatic lipocalins from <italic>Rhodnius prolixus<\/italic> and other blood-sucking arthropods","volume":"1482","author":"WR Montfort","year":"2000","journal-title":"Biochim Biophys Acta"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1056\/NEJM199308263290909","article-title":"American trypanosomiasis (Chagas&apos; disease)\u2013a tropical disease now in the United States","volume":"329","author":"LV Kirchhoff","year":"1993","journal-title":"N Engl J Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"8691","DOI":"10.1074\/jbc.270.15.8691","article-title":"Purification, partial characterization, and cloning of nitric oxide-carrying heme proteins (nitrophorins) from salivary glands of the blood-sucking insect <italic>Rhodnius prolixus<\/italic>","volume":"270","author":"DE Champagne","year":"1995","journal-title":"J Biol Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1021\/bi9628883","article-title":"Nitric oxide binding and crystallization of recombinant nitrophorin I, a nitric oxide transport protein from the blood-sucking bug <italic>Rhodnius prolixus<\/italic>","volume":"36","author":"JF Andersen","year":"1997","journal-title":"Biochemistry"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"30496","DOI":"10.1074\/jbc.M002857200","article-title":"The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein from the saliva of <italic>Rhodnius prolixus<\/italic>","volume":"275","author":"JF Andersen","year":"2000","journal-title":"J Biol Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/S0969-2126(98)00131-2","article-title":"The crystal structure of nitrophorin 4 at 1.5 A resolution: transport of nitric oxide by a lipocalin-based heme protein","volume":"6","author":"JF Andersen","year":"1998","journal-title":"Structure"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nsb0498-304","article-title":"Crystal structures of a nitric oxide transport protein from a blood-sucking insect","volume":"5","author":"A Weichsel","year":"1998","journal-title":"Nat Struct Mol Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/76769","article-title":"Nitric oxide binding to nitrophorin 4 induces complete distal pocket burial","volume":"7","author":"A Weichsel","year":"2000","journal-title":"Nat Struct Mol Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"13637","DOI":"10.1021\/bi0483155","article-title":"Protein functional cycle viewed at atomic resolution: conformational change and mobility in nitrophorin 4 as a function of pH and NO binding","volume":"43","author":"DA Kondrashov","year":"2004","journal-title":"Biochemistry"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"6679","DOI":"10.1021\/bi049748a","article-title":"Role of binding site loops in controlling nitric oxide release: structure and kinetics of mutant forms of nitrophorin 4","volume":"43","author":"EM Maes","year":"2004","journal-title":"Biochemistry"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1021\/ja075565a","article-title":"Bond or cage effect: how nitrophorins transport and release nitric oxide","volume":"130","author":"MA Mart\u00ed","year":"2008","journal-title":"J Am Chem Soc"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"5392","DOI":"10.1016\/j.febslet.2005.09.003","article-title":"Protonation state of Asp30 exerts crucial influence over surface loop rearrangements responsible for NO release in nitrophorin 4","volume":"579","author":"DK Menyh\u00e1rd","year":"2005","journal-title":"FEBS Lett"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1021\/jp808055e","article-title":"Molecular basis for the pH dependent structural transition of Nitrophorin 4","volume":"B113","author":"MA Mart\u00ed","year":"2009","journal-title":"J Phys Chem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1002\/jcc.20139","article-title":"Constant pH molecular dynamics in generalized Born implicit solvent","volume":"25","author":"J Mongan","year":"2004","journal-title":"J Comput Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jmb.2008.04.021","article-title":"Electrostatic effects in a network of polar and ionizable groups in staphylococcal nuclease","volume":"379","author":"KL Baran","year":"2008","journal-title":"J Mol Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"11566","DOI":"10.1021\/jp061190o","article-title":"Using a charging coordinate in studies of ionization induced partial unfolding","volume":"110","author":"M Kato","year":"2006","journal-title":"J Phys Chem B"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1529\/biophysj.108.130906","article-title":"Backbone relaxation coupled to the ionization of internal groups in proteins: a self-guided Langevin dynamics study","volume":"95","author":"A Damjanovi\u0107","year":"2008","journal-title":"Biophys J"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1063\/1.1497164","article-title":"Constant-pH molecular dynamics using stochastic titration","volume":"117","author":"AM Baptista","year":"2002","journal-title":"J Chem Phys"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"051911\/1","DOI":"10.1103\/PhysRevE.66.051911","article-title":"Langevin Dynamics of Proteins at Constant pH","volume":"66","author":"AM Walczak","year":"2002","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/prot.20128","article-title":"Constant-pH molecular dynamics using continuous titration coordinates","volume":"56","author":"MS Lee","year":"2004","journal-title":"Proteins"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1529\/biophysj.105.061341","article-title":"Constant pH molecular dynamics with proton tautomerism","volume":"89","author":"J Khandogin","year":"2005","journal-title":"Biophys J"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1016\/j.bpj.2012.02.021","article-title":"Thermodynamic Coupling of Protonation and Conformational Equilibria in Proteins: Theory and Simulation","volume":"102","author":"C Shi","year":"2012","journal-title":"Biophys J"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"12690","DOI":"10.1021\/bi0506573","article-title":"Ultrahigh resolution structures of nitrophorin 4: heme distortion in ferrous CO and NO complexes","volume":"44","author":"EM Maes","year":"2005","journal-title":"Biochemistry"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"39401","DOI":"10.1074\/jbc.M406178200","article-title":"Structural dynamics controls nitric oxide affinity in nitrophorin 4","volume":"279","author":"K Nienhaus","year":"2004","journal-title":"J Biol Chem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"9986","DOI":"10.1021\/ja2121662","article-title":"Heterogeneous kinetics of the carbon monoxide association and dissociation reaction of nitrophorin 4 and 7 coincide with structural heterogeneity of the gate-loop","volume":"134","author":"S Abbruzzetti","year":"2012","journal-title":"J Am Chem Soc"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1021\/ja910005b","article-title":"Ultrafast dynamics of diatomic ligand binding to nitrophorin 4","volume":"132","author":"A Benabbas","year":"2010","journal-title":"J Am Chem Soc"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1021\/jp806906x","article-title":"pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4","volume":"113","author":"JM Swails","year":"2009","journal-title":"J Phys Chem B"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1107\/S1744309111044708","article-title":"Crystallization and preliminary X-ray crystallographic analysis of the membrane-binding haemprotein nitrophorin 7 from <italic>Rhodnius prolixus<\/italic>","volume":"68","author":"H Ogata","year":"2012","journal-title":"Acta Cryst Sect F Struct Biol Cryst Commun"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1021\/ja01524a054","article-title":"Reversible transformation of \u03b2-lactoglobulin at pH 7.5","volume":"81","author":"C Tanford","year":"1959","journal-title":"J Am Chem Soc"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1021\/ja01468a022","article-title":"Ionization-linked Changes in Protein Conformation. II. The N\u2192R transition in \u03b2-lactoglobulin","volume":"83","author":"C Tanford","year":"1961","journal-title":"J Am Chem Soc"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"14014","DOI":"10.1021\/bi981016t","article-title":"Structural basis of the Tanford transition of bovine beta-lactoglobulin","volume":"37","author":"BY Qin","year":"1998","journal-title":"Biochemistry"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"5801","DOI":"10.1021\/bi900446j","article-title":"Crucial role of Asp408 in the proton translocation pathway of multidrug transporter AcrB: evidence from site-directed mutagenesis and carbodiimide labeling","volume":"48","author":"MA Seeger","year":"2009","journal-title":"Biochemistry"},{"key":"ref55","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":"ref56","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1073\/pnas.0510914103","article-title":"Multiconformation continuum electrostatics analysis of the NhaA Na+\/H+ antiporter of <italic>Escherichia coli<\/italic> with functional implications","volume":"103","author":"E Olkhova","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"10378","DOI":"10.1021\/bi00090a013","article-title":"Kinetics of Inactivation of the F1F0 ATPase of <italic>Propionigenium modestum<\/italic> by Dicyclohexylcarbodiimide in Relationship to H<sup>+<\/sup> and Na<sup>+<\/sup> Concentration: Probing the Binding Site for the Coupling Ions","volume":"32","author":"C Kluge","year":"1993","journal-title":"Biochemistry"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"16186","DOI":"10.1021\/bi00049a034","article-title":"Proton-Translocating Carboxyl of Subunit c of F1F0- H<sup>+<\/sup> ATP Synthas: The Unique Environment Suggested by the pKa determined by 1H NMR","volume":"34","author":"FM Assadi-Porter","year":"1995","journal-title":"Biochemistry"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.febslet.2004.08.049","article-title":"pKa of the essential Glu54 and backbone conformation for subunit c from the H+-coupled F1F0 ATP synthase from an alkaliphilic Bacillus","volume":"575","author":"IO Rivera-Torres","year":"2004","journal-title":"FEBS Lett"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/prot.22886","article-title":"Re-measuring HEWL pKa values by NMR spectroscopy: Methods, analysis, accuracy and implications for theoretical pKa calculations","volume":"79","author":"H Webb","year":"2011","journal-title":"Proteins"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1021\/bi00712a018","article-title":"The Acidic Transition of \u03b4-Chymotrypsin","volume":"13","author":"JR Garel","year":"1974","journal-title":"Biochemistry"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0300-9084(71)80076-7","article-title":"Rate of ligand-promoted isomerization of proteins. Relaxation study of the \u201calkaline-transition\u201d of \u03b4-chymotrypsin","volume":"53","author":"JR Garel","year":"1971","journal-title":"Biochimie"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0301-4622(75)80044-5","article-title":"The Alkaline Transition of Swine Pepsinogen","volume":"9","author":"P Mcphie","year":"1979","journal-title":"Biophys Chem"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0022-2836(72)90513-X","article-title":"Conformational Equilibria in alpha and delta Chymotrypsin","volume":"64","author":"AR Fersht","year":"1972","journal-title":"J Mol Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1063\/1.460602","article-title":"Generalized Langevin equations for molecular dynamics in solution","volume":"94","author":"T Xiang","year":"1991","journal-title":"J Chem Phys"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"JP Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/prot.21123","article-title":"Comparison of Multiple Amber Force Fields and Development of Improved Protein Backbone Parameters","volume":"725","author":"V Hornak","year":"2006","journal-title":"Proteins"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.1039\/B611741B","article-title":"Modeling heme proteins using atomistic simulations","volume":"8","author":"DE Bikiel","year":"2006","journal-title":"Phys Chem Chem Phys"},{"key":"ref69","unstructured":"Case DA, Darden TA, Cheatham TE, Simmerling CL, Wang J, <etal>et al<\/etal>.. (2010) AMBER 11. University of California, San Francisco (San Francisco)."},{"key":"ref70","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/prot.20033","article-title":"Exploring protein native states and large-scale conformational changes with a modified generalized born model","volume":"55","author":"A Onufriev","year":"2004","journal-title":"Proteins"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1063\/1.1699114","article-title":"Equation-of-state calculations by fast computing machines","volume":"21","author":"N Metropolis","year":"1953","journal-title":"J Chem Phys"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002761","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T20:01:13Z","timestamp":1714507273000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002761"}},"subtitle":[],"editor":[{"given":"James M.","family":"Briggs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,11,1]]},"references-count":71,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,11,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002761","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,1]]}}}