{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:41:36Z","timestamp":1772192496117,"version":"3.50.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2010,9,23]],"date-time":"2010-09-23T00:00:00Z","timestamp":1285200000000},"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.1000939","type":"journal-article","created":{"date-parts":[[2010,9,23]],"date-time":"2010-09-23T15:37:11Z","timestamp":1285256231000},"page":"e1000939","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":49,"title":["Molecular Dynamics Simulations Suggest that Electrostatic Funnel Directs Binding of Tamiflu to Influenza N1 Neuraminidases"],"prefix":"10.1371","volume":"6","author":[{"given":"Ly","family":"Le","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric H.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Hardy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanh N.","family":"Truong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Schulten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2010,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2217\/17460794.1.5.577","article-title":"Antiviral drugs for influenza: Tamiflu past, present and future.","volume":"5","author":"G Laver","year":"2006","journal-title":"Future Virol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/prot.340060402","article-title":"The neuraminidase of influenza virus.","volume":"6","author":"GM Air","year":"1989","journal-title":"Proteins"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1056\/NEJMra0707279","article-title":"Update on avian influenza A (H5N1) virus infection in humans.","volume":"358","author":"AN Abdel-Ghafar","year":"2008","journal-title":"N Engl J Med"},{"key":"ref4","first-page":"10","article-title":"Global tranmission of oseltamivir-resistant influenza.","volume":"360","author":"M A","year":"2009","journal-title":"N Engl J Med"},{"key":"ref5"},{"key":"ref6"},{"key":"ref7"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s00726-008-0201-z","article-title":"Source of oseltamivir resistance in avian influenza H5N1 virus with the h274y mutation.","volume":"37","author":"M Malaisree","year":"2009","journal-title":"Amino Acid"},{"key":"ref9","first-page":"131","article-title":"Comment on \u201canother look at the molecular mechanism of the resistance of h5n1 influenza a virus neuraminidase (NA) to oseltamivir (OTV)\u201d.","volume":"141","author":"T Rungrotmongkol","year":"2009","journal-title":"J Virol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/pro.77","article-title":"Computational studies of H5N1 influenza virus resistance to oseltamivir.","volume":"18","author":"XW Nick","year":"2009","journal-title":"Prot Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1021\/ci900348n","article-title":"Infiltration of water molecules into the oseltamivir-binding site of H274Y neuraminidase mutant causes resistance to oseltamivir.","volume":"29","author":"J Park","year":"2009","journal-title":"J Chem Inf Model"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/nature06956","article-title":"Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants.","volume":"453","author":"PJ Collins","year":"2008","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature05114","article-title":"The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design.","volume":"443","author":"RJ Russell","year":"2006","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.str.2008.05.016","article-title":"Bacteriophage lambda stabilization by auxiliary protein gpD: Timing, location, and mechanism of attachment determined by cryo-EM.","volume":"16","author":"GC Lander","year":"2008","journal-title":"Structure"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1021\/jm8001197","article-title":"Ensemble-based virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidase.","volume":"51","author":"LS Cheng","year":"2008","journal-title":"J Med Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1021\/ja9073672","article-title":"Role of secondary sialic acid binding sites in influenza n1 neuraminidase.","volume":"132","author":"JC Sung","year":"2010","journal-title":"J Am Chem Soc"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1021\/ja8085643","article-title":"Characterizing loop dynamics and ligand recognition in human- and avian-type influenza neuraminidases via generalized born molecular dynamics and end-point free energy calculations.","volume":"131","author":"RE Amaro","year":"2009","journal-title":"J Am Chem Soc"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1021\/ct800559d","article-title":"Independent-trajectories thermodynamic-integration free-energy changes for biomolecular systems: Determinants of H5N1 avian influenza virus neuraminidase inhibition by peramivir.","volume":"5","author":"M Lawrenz","year":"2009","journal-title":"J Chem Theor Comp"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1073\/pnas.90.11.5128","article-title":"An electrostatic mechanism for substrate guidance down the aromatic gorge of acetylcholinesterase.","volume":"90","author":"DR Ripoll","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1126\/science.8122110","article-title":"Open \u201cback door\u201d in a molecular dynamics simulation of acetylcholinesterase.","volume":"263","author":"MK Gilson","year":"1994","journal-title":"Science"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.parco.2008.12.005","article-title":"Multilevel summation of electrostatic potentials using graphics processing units.","volume":"35","author":"DJ Hardy","year":"2009","journal-title":"J Paral Comp"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1016\/S0006-3495(97)78804-0","article-title":"Molecular dynamics study of unbinding of the avidin-biotin complex.","volume":"72","author":"S Izrailev","year":"1997","journal-title":"Biophys J"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e8470","DOI":"10.1371\/journal.pone.0008470","article-title":"Steered molecular dynamics simulations reveal the likelier dissociation pathway of imatinib from its targeting kinases c-kit and abl.","volume":"4","author":"L Yang","year":"2009","journal-title":"PLoS One"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1021\/jp0716738","article-title":"Unbinding of nicotine from the acetylcholine binding protein: steered molecular dynamics simulations.","volume":"112","author":"X Liu","year":"2008","journal-title":"J Phys Chem B"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"10436","DOI":"10.1021\/jp903785h","article-title":"Computational insights into the mechanism of ligand unbinding and selectivity of estrogen receptors.","volume":"113","author":"J Shen","year":"2009","journal-title":"J Phys Chem B"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1063\/1.1590311","article-title":"Free energy calculation from steered molecular dynamics simulations using Jarzynski's equality.","volume":"119","author":"S Park","year":"2003","journal-title":"J Chem Phys"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"5946","DOI":"10.1063\/1.1651473","article-title":"Calculating potentials of mean force from steered molecular dynamics simulations.","volume":"120","author":"S Park","year":"2004","journal-title":"J Chem Phys"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1747-0285.2007.00614.x","article-title":"Novel druggable hot spots in avian influenza neuraminidase H5N1 revealed by computational solvent mapping of a reduced and representative receptor ensemble.","volume":"71","author":"MR Landon","year":"2008","journal-title":"Chem Biol Drug Des"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"7764","DOI":"10.1021\/ja0723535","article-title":"Remarkable loop exibility in avian influenza N1 and its implications for antiviral drug design.","volume":"129","author":"RE Amaro","year":"2007","journal-title":"J Am Chem Soc"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"8787","DOI":"10.1128\/JVI.00477-06","article-title":"Importance of neuraminidase active-site residues to the neuraminidase inhibitor resistance of influenza viruses.","volume":"80","author":"H Yen","year":"2006","journal-title":"J Virol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1021\/ct800068v","article-title":"Origins of resistance conferred by the R292K neuraminidase mutation via molecular dynamics and free energy calculations.","volume":"4","author":"R Chachra","year":"2008","journal-title":"J Chem Theor Comp"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1177\/135965350601100804","article-title":"Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the n1 and n2 genetic backgrounds.","volume":"11","author":"A Y","year":"2006","journal-title":"Antiviral Ther"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.1021\/jm0002679","article-title":"Bcx-1812 (rwj-270201): Discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design.","volume":"43","author":"YS Babu","year":"2000","journal-title":"J Med Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1517\/14728214.13.3.393","article-title":"Emerging antiviral drugs.","volume":"13","author":"ED Clercq","year":"2008","journal-title":"Expert Opin Emerging Drugs"},{"key":"ref35","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 Graphics"},{"key":"ref36","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":"ref37","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/jcc.20065","article-title":"Extending the treatment of backbone energetics in protein force fields: Limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations.","volume":"25","author":"AD MacKerell Jr","year":"2004","journal-title":"J Comp Chem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"L36","DOI":"10.1529\/biophysj.105.078154","article-title":"Importance of the CMAP correction to the CHARMM22 protein force field: Dynamics of hen lysozyme.","volume":"90","author":"M Buck","year":"2006","journal-title":"Biophys J"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"13319","DOI":"10.1073\/pnas.0702401104","article-title":"Molecular dioxygen enters the active site of 12\/15 lipoxygenase via dynamic oxygen access channels.","volume":"104","author":"J Saam","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref40","article-title":"Gaussian 03 (Revision B.05).","author":"MJ Frisch","year":"2003"},{"key":"ref41","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 Comp Chem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0959-440X(00)00194-9","article-title":"Steered molecular dynamics and mechanical functions of proteins.","volume":"11","author":"B Isralewitz","year":"2001","journal-title":"Curr Opin Struct Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.1039\/b606019f","article-title":"Molecular mechanisms of cellular mechanics.","volume":"8","author":"M Gao","year":"2006","journal-title":"Phys Chem Chem Phys"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1529\/biophysj.106.095232","article-title":"Ion conduction through MscS as determined by electrophysiology and simulation.","volume":"92","author":"M Sotomayor","year":"2007","journal-title":"Biophys J"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1073\/pnas.0706075105","article-title":"Solvent molecules bridge the mechanical unfolding transition state of a protein.","volume":"105","author":"L Dougan","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.str.2009.09.001","article-title":"Discovery through the computational microscope.","volume":"17","author":"EH Lee","year":"2009","journal-title":"Structure"},{"key":"ref47","first-page":"141","article-title":"Mechanical signaling on the single protein level studied using steered molecular dynamics.","volume":"55","author":"G Genchev","year":"2009"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0006-3495(97)78802-7","article-title":"Dynamic strength of molecular adhesion bonds.","volume":"72","author":"E Evans","year":"1997","journal-title":"Biophys J"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jcc.10072","article-title":"Multiple grid methods for classical molecular dynamics.","volume":"23","author":"RD Skeel","year":"2002","journal-title":"J Comp Chem"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1073\/pnas.181342398","article-title":"Electrostatics of nanosystems: Application to microtubules and the ribosome.","volume":"98","author":"NA Baker","year":"2001","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T14:32:47Z","timestamp":1711809167000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000939"}},"subtitle":[],"editor":[{"given":"Rommie E.","family":"Amaro","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2010,9,23]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2010,9,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000939","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.6320958.6415061","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,23]]}}}