{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:03:07Z","timestamp":1787954587524,"version":"build-2784847793"},"reference-count":57,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2005,2,1]],"date-time":"2005-02-01T00:00:00Z","timestamp":1107216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2005,2,1]],"date-time":"2005-02-01T00:00:00Z","timestamp":1107216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"content-version":"vor","delay-in-days":3087,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2005,2]]},"DOI":"10.1529\/biophysj.104.049882","type":"journal-article","created":{"date-parts":[[2004,11,19]],"date-time":"2004-11-19T20:14:03Z","timestamp":1100895243000},"page":"1334-1343","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":53,"title":["Misfolding Pathways of the Prion Protein Probed by Molecular Dynamics Simulations"],"prefix":"10.1016","volume":"88","author":[{"given":"Alessandro","family":"Barducci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Chelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Procacci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Schettino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1529\/biophysj.104.049882_bib1","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1073\/pnas.061555898","article-title":"Mapping the early steps in the pH-induced conformational conversion of the prion protein","volume":"98","author":"Alonso","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0022-2836(77)80200-3","article-title":"The Protein Data Bank: a computer based archival file for macromolecular structures","volume":"112","author":"Bernstein","year":"1977","journal-title":"J. Mol. Biol."},{"key":"10.1529\/biophysj.104.049882_bib3","doi-asserted-by":"crossref","first-page":"35592","DOI":"10.1074\/jbc.M303005200","article-title":"Influence of pH on NMR structure and stability of the human prion protein globular domain","volume":"278","author":"Calzolai","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.049882_bib4","doi-asserted-by":"crossref","first-page":"7672","DOI":"10.1021\/bi00245a003","article-title":"Secondary structure-analysis of the scrapie-associated protein PrP 27\u201330 in water by infrared-spectroscopy","volume":"30","author":"Caughey","year":"1991","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.049882_bib5","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1021\/ja00119a045","article-title":"Molecular-dynamics simulations on solvated biomolecular systems\u2014the particle mesh Ewald method leads to stable trajectories of DNA, RNA, and proteins","volume":"117","author":"Cheatham","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"10.1529\/biophysj.104.049882_bib6","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1021\/ja00124a002","article-title":"A 2nd generation force-field for the simulation of proteins, nucleic-acids, and organic-molecules","volume":"117","author":"Cornell","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"10.1529\/biophysj.104.049882_bib7","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1073\/pnas.0307178101","article-title":"From conversion to aggregation: protofibril formation of the prion protein","volume":"101","author":"DeMarco","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib8","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1126\/science.282.5389.740","article-title":"Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution","volume":"282","author":"Duan","year":"1998","journal-title":"Science"},{"key":"10.1529\/biophysj.104.049882_bib9","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/jcc.10349","article-title":"A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations","volume":"24","author":"Duan","year":"2003","journal-title":"J. Comput. Chem."},{"key":"10.1529\/biophysj.104.049882_bib10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S1093-3263(01)00113-9","article-title":"Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature","volume":"20","author":"El Bastawissy","year":"2001","journal-title":"J. Mol. Graph. Model."},{"key":"10.1529\/biophysj.104.049882_bib11","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"10.1529\/biophysj.104.049882_bib12","doi-asserted-by":"crossref","first-page":"8070","DOI":"10.1021\/jp9717655","article-title":"Application of the RESP methodology in the parametrization of organic solvents","volume":"102","author":"Fox","year":"1998","journal-title":"J. Phys. Chem. B"},{"key":"10.1529\/biophysj.104.049882_bib13","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1146\/annurev.bb.17.060188.002315","article-title":"Conformational substates in proteins","volume":"17","author":"Fraunfelder","year":"1988","journal-title":"Annu. Rev. Biophys. Biophys. Chem."},{"key":"10.1529\/biophysj.104.049882_bib14","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1073\/pnas.042496899","article-title":"\u03b1-helical stabilization by side chain shielding of backbone hydrogen bonds","volume":"99","author":"Garcia","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1093-3263(01)00117-6","article-title":"Flexibility of the murine prion protein and its Asp178Asn mutant investigated by molecular dynamics simulations","volume":"20","author":"Gsponer","year":"2001","journal-title":"J. Mol. Graph. Model."},{"key":"10.1529\/biophysj.104.049882_bib16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0301-4622(02)00340-X","article-title":"Molecular dynamics simulation of the unfolding of the human prion protein domain under low pH and high temperature conditions","volume":"104","author":"Gu","year":"2003","journal-title":"Biophys. Chem."},{"key":"10.1529\/biophysj.104.049882_bib17","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/1097-0282(200011)54:6<406::AID-BIP50>3.0.CO;2-6","article-title":"Dynamic simulation of the mouse prion protein","volume":"54","author":"Guilbert","year":"2000","journal-title":"Biopolymers"},{"key":"10.1529\/biophysj.104.049882_bib18","doi-asserted-by":"crossref","first-page":"6010","DOI":"10.1073\/pnas.95.11.6010","article-title":"A scrapie-like unfolding intermediate of the prion protein domain PrP(121\u2013231) induced by acidic pH","volume":"95","author":"Hornemann","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S1359-0278(96)00007-7","article-title":"Scrapie prions: a three-dimensional model of an infectious fragment","volume":"1","author":"Huang","year":"1996","journal-title":"Fold. Des."},{"key":"10.1529\/biophysj.104.049882_bib20","doi-asserted-by":"crossref","first-page":"10086","DOI":"10.1073\/pnas.94.19.10086","article-title":"Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform","volume":"94","author":"James","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib21","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":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"10.1529\/biophysj.104.049882_bib22","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":"Kabsch","year":"1983","journal-title":"Biopolymers"},{"key":"10.1529\/biophysj.104.049882_bib23","doi-asserted-by":"crossref","first-page":"12562","DOI":"10.1073\/pnas.202427399","article-title":"Escaping free-energy minima","volume":"99","author":"Laio","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib24","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1021\/bi982714g","article-title":"Influence of amino acid substitutions related to inherited human prion diseases on the thermodynamic stability of the cellular prion protein","volume":"38","author":"Liemann","year":"1999","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.049882_bib25","doi-asserted-by":"crossref","first-page":"5362","DOI":"10.1021\/bi982878x","article-title":"Solution structure of Syrian hamster prion protein rPrP(90\u2013231)","volume":"38","author":"Liu","year":"1999","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.049882_bib26","doi-asserted-by":"crossref","first-page":"8334","DOI":"10.1073\/pnas.97.15.8334","article-title":"NMR structure of the bovine prion protein","volume":"97","author":"Lopez Garcia","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib27","doi-asserted-by":"crossref","first-page":"5194","DOI":"10.1063\/1.477136","article-title":"Coordinates scaling and multiple time step algorithms for simulation of solvated proteins in the NPT ensemble","volume":"109","author":"Marchi","year":"1998","journal-title":"J. Chem. Phys."},{"key":"10.1529\/biophysj.104.049882_bib28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00214-004-0565-4","article-title":"The influence of simulation conditions in molecular dynamics investigations of model \u03b2-sheet peptides","volume":"112","author":"Monticelli","year":"2004","journal-title":"Theor. Chem. Acc."},{"key":"10.1529\/biophysj.104.049882_bib29","doi-asserted-by":"crossref","first-page":"5064","DOI":"10.1021\/jp022445a","article-title":"Conformational dynamics of trialanine in water. 2. Comparison of AMBER, CHARMM, GROMOS, and OPLS force fields to NMR and infrared experiments","volume":"107","author":"Mu","year":"2003","journal-title":"J. Phys. Chem. B"},{"key":"10.1529\/biophysj.104.049882_bib30","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1006\/jmbi.1995.0507","article-title":"X-ray-diffraction of scrapie prion rods and PrP peptides","volume":"252","author":"Nguyen","year":"1995","journal-title":"J. Mol. Biol."},{"key":"10.1529\/biophysj.104.049882_bib31","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1080\/00268978400101201","article-title":"A molecular dynamics method for simulations in the canonical ensemble","volume":"52","author":"Nos\u00e9","year":"1984","journal-title":"Molec. Phys."},{"key":"10.1529\/biophysj.104.049882_bib32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/jcc.10184","article-title":"Using PC clusters to evaluate the transferability of molecular mechanics force fields for proteins","volume":"24","author":"Okur","year":"2003","journal-title":"J. Comput. Chem."},{"key":"10.1529\/biophysj.104.049882_bib33","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.90.23.10962","article-title":"Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins","volume":"90","author":"Pan","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib34","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/(SICI)1097-0134(20000215)38:3<327::AID-PROT8>3.0.CO;2-G","article-title":"Molecular dynamics of mouse and Syrian hamster PrP: implications for activity","volume":"38","author":"Parchment","year":"2000","journal-title":"Proteins"},{"key":"10.1529\/biophysj.104.049882_bib35","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1016\/S0006-3495(03)75094-2","article-title":"Molecular dynamics simulations of lipid bilayers: major artifacts due to truncating electrostatic interactions","volume":"84","author":"Patra","year":"2003","journal-title":"Biophys. J."},{"key":"10.1529\/biophysj.104.049882_bib36","doi-asserted-by":"crossref","first-page":"10464","DOI":"10.1021\/jp960295w","article-title":"A very fast molecular dynamics method to simulate biomolecular systems with realistic electrostatic interactions","volume":"100","author":"Procacci","year":"1996","journal-title":"J. Phys. Chem."},{"key":"10.1529\/biophysj.104.049882_bib37","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1002\/(SICI)1096-987X(19971130)18:15<1848::AID-JCC2>3.0.CO;2-O","article-title":"ORAC: a molecular dynamics program to simulate complex molecular systems with realistic electrostatic interactions","volume":"18","author":"Procacci","year":"1997","journal-title":"J. Comput. Chem."},{"key":"10.1529\/biophysj.104.049882_bib38","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1126\/science.6801762","article-title":"Novel proteinaceous infectious particles cause scrapie","volume":"216","author":"Prusiner","year":"1982","journal-title":"Science"},{"key":"10.1529\/biophysj.104.049882_bib39","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S0968-0004(96)10063-3","article-title":"Molecular biology and pathogenesis of prion diseases","volume":"21","author":"Prusiner","year":"1996","journal-title":"Trends Biochem. Sci."},{"key":"10.1529\/biophysj.104.049882_bib40","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Prions","volume":"95","author":"Prusiner","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib41","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0092-8674(83)90168-X","article-title":"Scrapie prions aggregate to form amyloid-like birefringent rods","volume":"35","author":"Prusiner","year":"1983","journal-title":"Cell"},{"key":"10.1529\/biophysj.104.049882_bib42","doi-asserted-by":"crossref","first-page":"6675","DOI":"10.1073\/pnas.78.11.6675","article-title":"Scrapie agent contains a hydrophobic protein","volume":"78","author":"Prusiner","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib43","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/382180a0","article-title":"NMR structure of the mouse prion protein domain PrP(121\u2013231)","volume":"382","author":"Riek","year":"1996","journal-title":"Nature"},{"key":"10.1529\/biophysj.104.049882_bib44","doi-asserted-by":"crossref","first-page":"11667","DOI":"10.1073\/pnas.95.20.11667","article-title":"Prion protein NMR structure and familial human spongiform encephalopathies","volume":"95","author":"Riek","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib45","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1063\/1.468411","article-title":"Molecular-dynamics simulations of proteins in solution\u2014artifacts caused by the cutoff approximation","volume":"101","author":"Saito","year":"1994","journal-title":"J. Chem. Phys."},{"key":"10.1529\/biophysj.104.049882_bib46","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/S0006-3495(03)74553-6","article-title":"Molecular dynamics simulation of dimeric and monomeric forms of human prion protein: insight into dynamics and properties","volume":"85","author":"Sekijima","year":"2003","journal-title":"Biophys. J."},{"key":"10.1529\/biophysj.104.049882_bib47","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1096\/fasebj.5.13.1916104","article-title":"Prions and prion proteins","volume":"5","author":"Stahl","year":"1991","journal-title":"FASEB J."},{"key":"10.1529\/biophysj.104.049882_bib48","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1021\/bi991967m","article-title":"Aggregation and fibrillization of the recombinant human prion protein huPrP90\u2013231","volume":"39","author":"Swietnicki","year":"2000","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.049882_bib49","doi-asserted-by":"crossref","first-page":"27517","DOI":"10.1074\/jbc.272.44.27517","article-title":"pH-dependent stability and conformation of the recombinant human prion protein PrP(90\u2013231)","volume":"272","author":"Swietnicki","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.049882_bib50","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1063\/1.463137","article-title":"Reversibile multiple time scale molecular-dynamics","volume":"97","author":"Tuckerman","year":"1992","journal-title":"J. Chem. Phys."},{"key":"10.1529\/biophysj.104.049882_bib51","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1432-1033.1988.tb14246.x","article-title":"Purification and properties of the cellular and scrapie Hamster prion proteins","volume":"176","author":"Turk","year":"1988","journal-title":"Eur. J. Biochem."},{"key":"10.1529\/biophysj.104.049882_bib52","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1073\/pnas.052703499","article-title":"Structural studies of the scrapie prion protein by electron crystallography","volume":"99","author":"Wille","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib53","doi-asserted-by":"crossref","first-page":"8254","DOI":"10.1063\/1.478738","article-title":"Exact method for the simulation of Coulombic systems by spherically truncated, pairwise r\u22121 summation","volume":"110","author":"Wolf","year":"1999","journal-title":"J. Chem. Phys."},{"key":"10.1529\/biophysj.104.049882_bib54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1073\/pnas.97.1.145","article-title":"NMR solution structure of the human prion protein","volume":"97","author":"Zahn","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.049882_bib55","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/S0022-2836(03)00765-4","article-title":"Investigations into sequence and conformational dependence of backbone entropy, inter-basin dynamics and the Flory isolated-pair hypothesis for peptides","volume":"331","author":"Zaman","year":"2003","journal-title":"J. Mol. Biol."},{"key":"10.1529\/biophysj.104.049882_bib56","doi-asserted-by":"crossref","first-page":"50175","DOI":"10.1074\/jbc.M305234200","article-title":"CD and NMR studies of prion protein (PrP) helix 1: novel implications for its role in the PrPC \u2192 PrPSC conversion process","volume":"278","author":"Ziegler","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.049882_bib57","doi-asserted-by":"crossref","first-page":"43942","DOI":"10.1074\/jbc.M203611200","article-title":"Acidic pH and detergents enhance in vitro conversion of human brain PrPC to a PrPSC-like form","volume":"277","author":"Zou","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349505731994?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349505731994?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:17:30Z","timestamp":1762100250000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006349505731994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,2]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2005,2]]}},"alternative-id":["S0006349505731994"],"URL":"https:\/\/doi.org\/10.1529\/biophysj.104.049882","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2005,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Misfolding Pathways of the Prion Protein Probed by Molecular Dynamics Simulations","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1529\/biophysj.104.049882","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2005 The Biophysical Society. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}