{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T15:07:20Z","timestamp":1770131240728,"version":"3.49.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T00:00:00Z","timestamp":1294272000000},"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.1001053","type":"journal-article","created":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T22:20:18Z","timestamp":1294352418000},"page":"e1001053","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["Predicting Novel Binding Modes of Agonists to \u03b2 Adrenergic Receptors Using All-Atom Molecular Dynamics Simulations"],"prefix":"10.1371","volume":"7","author":[{"given":"Stefano","family":"Vanni","sequence":"first","affiliation":[]},{"given":"Marilisa","family":"Neri","sequence":"additional","affiliation":[]},{"given":"Ivano","family":"Tavernelli","sequence":"additional","affiliation":[]},{"given":"Ursula","family":"Rothlisberger","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2011,1,6]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/sj.tpj.6500393","article-title":"Pharmacogenetics of the human beta-adrenergic receptors.","volume":"7","author":"MRG Taylor","year":"2007","journal-title":"Pharmacogenomics J"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00210-003-0860-y","article-title":"Comparative pharmacology of human beta-adrenergic receptor subtypes - characterization of stably transfected receptors in CHO cells.","volume":"369","author":"C Hoffmann","year":"2004","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1126\/science.1150577","article-title":"High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor.","volume":"318","author":"V Cherezov","year":"2007","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature07101","article-title":"Structure of a beta1-adrenergic G-protein-coupled receptor.","volume":"454","author":"T Warne","year":"2008","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"10267","DOI":"10.1016\/S0021-9258(19)81509-0","article-title":"Conserved Aspartic Acid Residues 79 and 113 of the beta-Adrenergic Receptor Have Different Roles in Receptor Function.","volume":"263","author":"CD Strader","year":"1988","journal-title":"J Biol Chem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"13572","DOI":"10.1016\/S0021-9258(18)80035-7","article-title":"Identification of 2 serine residues involved in agonist activation of the beta-adrenergic-receptor.","volume":"264","author":"CD Strader","year":"1989","journal-title":"J Biol Chem"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0026-895X(25)13115-5","article-title":"Amino-acid substitutions at position 312 in the 7th hydrophobic segment of the beta(2)-adrenergic receptor modify ligand-binding specificity.","volume":"44","author":"S Suryanarayana","year":"1993","journal-title":"Mol Pharmacol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"9276","DOI":"10.1073\/pnas.93.17.9276","article-title":"Involvement of Asn-293 in stereospecific agonist recognition and in activation of the beta2-adrenergic receptor.","volume":"93","author":"K Wieland","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/S0026-895X(24)13061-1","article-title":"Identification of a key amino acid of the beta(2)-adrenergic receptor for high affinity binding of salmeterol.","volume":"54","author":"M Isogaya","year":"1998","journal-title":"Mol Pharmacol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"37779","DOI":"10.1074\/jbc.M002092200","article-title":"The forgotten serine - A critical role for Ser-203(5.42) in ligand binding to and activation of the beta(2)-adrenergic receptor.","volume":"275","author":"G Liapakis","year":"2000","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.1021\/jm800710x","article-title":"Selective Structure-Based Virtual Screening for Full and Partial Agonists of the Beta2 Adrenergic Receptor.","volume":"51","author":"C de Graaf","year":"2008","journal-title":"J Med Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nchembio.97","article-title":"Insights into signaling from the \u03b22-adrenergic receptor structure.","volume":"4","author":"M Audet","year":"2008","journal-title":"Nat Chem Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/jmr.949","article-title":"Analysis of full and partial agonists binding to beta2-adrenergic receptor suggests a role of transmembrane helix V in agonist-specific conformational changes.","volume":"22","author":"V Katritch","year":"2009","journal-title":"J Mol Recognit"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"6843","DOI":"10.1073\/pnas.0812657106","article-title":"Structure-based discovery of beta2-adrenergic receptor ligands.","volume":"106","author":"P Kolb","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/jcc.21346","article-title":"Ligand and Structure-Based Models for the Prediction of Ligand-Receptor Affinitie and Virtual Screenings: Development and Application to the Beta2-Adrenergic Receptor.","volume":"31","author":"S Vilar","year":"2010","journal-title":"J Comput Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s10822-008-9257-9","article-title":"Identifying conformational changes of the beta2 adrenoceptor that enable accurate prediction of ligand\/receptor interactions and screening for GPCR modulators.","volume":"23","author":"KA Reynolds","year":"2009","journal-title":"J Comput Aided Mol Des"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"22165","DOI":"10.1074\/jbc.M502352200","article-title":"Probing the beta(2) adrenoreceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists.","volume":"280","author":"G Swaminath","year":"2005","journal-title":"J Biol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nchembio801","article-title":"Coupling ligand structure to specific conformational switches in the beta(2)-adrenoreceptor.","volume":"2","author":"XJ Yao","year":"2006","journal-title":"Nat Chem Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"24433","DOI":"10.1074\/jbc.C100162200","article-title":"Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta(2) adrenergic receptor.","volume":"276","author":"P Ghanouni","year":"2001","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.tips.2007.06.003","article-title":"Conformational complexity of G-protein-coupled receptors.","volume":"28","author":"BK Kobilka","year":"2007","journal-title":"Trends Pharmacol Sci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"9501","DOI":"10.1073\/pnas.0811437106","article-title":"The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex.","volume":"106","author":"XJ Yao","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1074\/jbc.275.5.3121","article-title":"The Effect of pH on Beta2 Adrenoceptor Function.","volume":"275","author":"P Ghanouni","year":"2000","journal-title":"J Biol Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1038\/emboj.2009.267","article-title":"Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer.","volume":"28","author":"JJ Fung","year":"2009","journal-title":"EMBO Journal"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nsmb.1549","article-title":"Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation.","volume":"16","author":"S Ahuja","year":"2009","journal-title":"Nat Struct Mol Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature08650","article-title":"Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor.","volume":"463","author":"MP Bokoch","year":"2010","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/cbic.200600429","article-title":"The Role of Internal Water Molecules in the Structure and Function of the Rhodopsin Family of G Protein-Coupled Receptors.","volume":"8","author":"L Pardo","year":"2007","journal-title":"Chembiochem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"14367","DOI":"10.1073\/pnas.0901074106","article-title":"Structural waters define a functional channel mediating activation of the GPCR, rhodopsin.","volume":"106","author":"TE Angel","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"19625","DOI":"10.1074\/jbc.M110.106021","article-title":"Conserved water-mediated hydrogen bond network between TM-I,-II,-VI and -VII in 7TM receptor activation.","volume":"285","author":"R Nygaard","year":"2010","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"8374","DOI":"10.1021\/jp909971f","article-title":"Molecular dynamics simulations reveal fundamental role of water as factor determining affinity of binding of bet-blocker nebivolol to beta(2)-adrenergic receptor.","volume":"114","author":"K Kaszuba","year":"2010","journal-title":"J Phys Chem B"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.jmb.2010.01.060","article-title":"A conserved protonation-induced switch can trigger \u201cionic lock\u201d formation in adrenergic receptors.","volume":"397","author":"S Vanni","year":"2010","journal-title":"J Mol Biol"},{"key":"ref31","first-page":"331","article-title":"Interaction models for water in relation to protein hydration. Intermolecular Forces","author":"HJC Berendsen","year":"1981"},{"key":"ref32","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":"WD Cornell","year":"1995","journal-title":"J Am Chem Soc"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"10269","DOI":"10.1021\/j100142a004","article-title":"A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges - The RESP model.","volume":"97","author":"CI Bayly","year":"1993","journal-title":"J Phys Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/1096-987X(200009)21:12<1049::AID-JCC3>3.0.CO;2-F","article-title":"How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules?","volume":"21","author":"JM Wang","year":"2000","journal-title":"J Comput Chem"},{"key":"ref35","article-title":"Gaussian 03","author":"MJ Frisch","year":"2004"},{"key":"ref36","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":"ref37","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":"ref38","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":"ref39","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1080\/00268978600100141","article-title":"An extension of the canonical ensemble molecular-dynamics method.","volume":"57","author":"S Nose","year":"1986","journal-title":"Mol Phys"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","article-title":"Canonical dynamics - equilibrium phase-space distributions.","volume":"31","author":"WG Hoover","year":"1985","journal-title":"Phys Rev A"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single-crystals - A new molecular-dynamics method.","volume":"52","author":"M Parrinello","year":"1981","journal-title":"J Appl Phys"},{"key":"ref42","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":"ref43","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/281114a0","article-title":"Fundamental difference between the molecular interactions of agonists and antagonists with the beta-adrenergic receptor.","volume":"281","author":"GA Weiland","year":"1979","journal-title":"Nature"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1021\/bi900299f","article-title":"Observation of \u201cIonic Lock\u201d Formation in Molecular Dynamics Simulations of Wild-Type Beta1 and Beta2 Adrenergic Receptors.","volume":"48","author":"S Vanni","year":"2009","journal-title":"Biochemistry"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bpj.2009.09.046","article-title":"Concerted Interconversion between Ionic Lock Substates of the Beta2 Adrenergic Receptor Revealed by Microsecond Timescale Molecular Dynamics.","volume":"98","author":"TD Romo","year":"2010","journal-title":"Biophys J"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1074\/jbc.M310888200","article-title":"Sequential binding of agonists to the beta2 adrenoceptor. Kinetic evidence for intermediate conformational states.","volume":"279","author":"G Swaminath","year":"2004","journal-title":"J Biol Chem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1124\/mol.108.048371","article-title":"Role of Key Transmembrane Residues in Agonist and Antagonist Actions at the Two Conformations of the Human Beta(1)-Adrenoceptor.","volume":"74","author":"JG Baker","year":"2008","journal-title":"Mol Pharmacol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1016\/S0021-9258(18)68888-X","article-title":"Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation.","volume":"263","author":"FZ Chung","year":"1988","journal-title":"J Biol Chem"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1248\/bpb.31.1517","article-title":"Mutation of Important Amino Acid Residue of Asp104Lys in Human Beta1-Adrenergic Receptor Triggers Functional and Constitutive Inactivation.","volume":"31","author":"M Hossain","year":"2008","journal-title":"Biol Pharm Bull"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.jmb.2009.07.093","article-title":"Ligand Entry and Exit Pathways in the Beta2- Adrenergic Receptor.","volume":"392","author":"T Wang","year":"2009","journal-title":"J Mol Biol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"11013","DOI":"10.1021\/bi800891r","article-title":"Structural Basis for Ligand Binding and Specificity in Adrenergic Receptors: Implications for GPCR-Targeted Drug Discovery.","volume":"47","author":"T Huber","year":"2008","journal-title":"Biochemistry"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1001053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T13:37:15Z","timestamp":1740836235000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1001053"}},"subtitle":[],"editor":[{"given":"James M.","family":"Briggs","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2011,1,6]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2011,1,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1001053","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,6]]}}}