{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:15:30Z","timestamp":1770275730827,"version":"3.49.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2014,12,11]],"date-time":"2014-12-11T00:00:00Z","timestamp":1418256000000},"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.1004006","type":"journal-article","created":{"date-parts":[[2014,12,11]],"date-time":"2014-12-11T19:00:37Z","timestamp":1418324437000},"page":"e1004006","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["Molecular Insights into the Dynamics of Pharmacogenetically Important N-Terminal Variants of the Human \u03b22-Adrenergic Receptor"],"prefix":"10.1371","volume":"10","author":[{"given":"Ganesh","family":"Shahane","sequence":"first","affiliation":[]},{"given":"Chirag","family":"Parsania","sequence":"additional","affiliation":[]},{"given":"Durba","family":"Sengupta","sequence":"additional","affiliation":[]},{"given":"Manali","family":"Joshi","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2014,12,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S0165-6147(00)01678-3","article-title":"G-protein-coupled receptors and signaling networks: emerging paradigms","volume":"22","author":"MJ Marinissen","year":"2001","journal-title":"Trends Pharmacol Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrm908","article-title":"Seven-transmembrane receptors","volume":"3","author":"KL Pierce","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-1-60327-317-6_4","article-title":"An overview on GPCRs and drug discovery: structure-based drug design and structural biology on GPCRs","volume":"552","author":"K Lundstrom","year":"2009","journal-title":"Method Mol Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature08144","article-title":"The structure and function of G-protein-coupled receptors","volume":"459","author":"DM Rosenbaum","year":"2009","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/nrd2199","article-title":"How many drug targets are there","volume":"5","author":"JP Overington","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jaci.2005.11.012","article-title":"Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation","volume":"117","author":"M Johnson","year":"2006","journal-title":"J Allergy Clin Immunol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1146\/annurev.bi.52.070183.001111","article-title":"Adenylate cyclase-coupled beta-adrenergic receptors: structure and mechanisms of activation and desensitization","volume":"52","author":"RJ Lefkowitz","year":"1983","journal-title":"Annu Rev Biochem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.pcrj.2006.09.002","article-title":"A brief history of inhaled asthma therapy over the last fifty years","volume":"15","author":"G Crompton","year":"2006","journal-title":"Prim Care Respir J"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"32899","DOI":"10.1074\/jbc.R110.206466","article-title":"Biochemical basis of asthma therapy","volume":"286","author":"PJ Barnes","year":"2011","journal-title":"J Biol Chem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1165\/ajrcmb\/8.3.334","article-title":"Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects","volume":"8","author":"E Reihsaus","year":"1993","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref11","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":"MR Taylor","year":"2007","journal-title":"Pharmacogenomics J"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/FPC.0b013e328333dae6","article-title":"Very important pharmacogene summary ADRB2","volume":"20","author":"AA Litonjua","year":"2010","journal-title":"Pharmacogenet Genom"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2217\/14622416.9.5.505","article-title":"Pharmacogenetic response to albuterol among asthmatics","volume":"9","author":"H Corvol","year":"2008","journal-title":"Pharmacogenomics"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"ra53","DOI":"10.1126\/scisignal.2001681","article-title":"A polymorphism-specific "memory" mechanism in the beta(2)-adrenergic receptor","volume":"4","author":"A Ahles","year":"2011","journal-title":"Sci Signal"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"9414","DOI":"10.1021\/bi00198a006","article-title":"Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties","volume":"33","author":"SA Green","year":"1994","journal-title":"Biochemistry"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nature06325","article-title":"Crystal structure of the human beta2 adrenergic G-protein-coupled receptor","volume":"450","author":"SG Rasmussen","year":"2007","journal-title":"Nature"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1126\/science.1150609","article-title":"GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function","volume":"318","author":"DM Rosenbaum","year":"2007","journal-title":"Science"},{"key":"ref18","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":"ref19","doi-asserted-by":"crossref","first-page":"11443","DOI":"10.1021\/ja105108q","article-title":"Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography","volume":"132","author":"D Wacker","year":"2010","journal-title":"J Am Chem Soc"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1126\/science.1215904","article-title":"Crystal structure of a lipid G protein-coupled receptor","volume":"335","author":"MA Hanson","year":"2012","journal-title":"Science"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nature09648","article-title":"Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor","volume":"469","author":"SG Rasmussen","year":"2011","journal-title":"Nature"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature10361","article-title":"Crystal structure of the beta2 adrenergic receptor-Gs protein complex","volume":"477","author":"SG Rasmussen","year":"2011","journal-title":"Nature"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature09665","article-title":"Structure and function of an irreversible agonist-beta(2) adrenoceptor complex","volume":"469","author":"DM Rosenbaum","year":"2011","journal-title":"Nature"},{"key":"ref24","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":"ref25","doi-asserted-by":"crossref","first-page":"18684","DOI":"10.1073\/pnas.1110499108","article-title":"Activation mechanism of the beta2-adrenergic receptor","volume":"108","author":"RO Dror","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"13118","DOI":"10.1073\/pnas.1104614108","article-title":"Pathway and mechanism of drug binding to G-protein-coupled receptors","volume":"108","author":"RO Dror","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nchem.1821","article-title":"Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways","volume":"6","author":"KJ Kohlhoff","year":"2014","journal-title":"Nat Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"D309","DOI":"10.1093\/nar\/gkq1009","article-title":"GPCRDB: information system for G protein-coupled receptors","volume":"39","author":"B Vroling","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/prot.340230412","article-title":"Knowledge-based protein secondary structure assignment","volume":"23","author":"D Frishman","year":"1995","journal-title":"Proteins"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e23815","DOI":"10.1371\/journal.pone.0023815","article-title":"Molecular basis of ligand dissociation in beta-adrenergic receptors","volume":"6","author":"A Gonzalez","year":"2011","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature11896","article-title":"Molecular signatures of G-protein-coupled receptors","volume":"494","author":"AJ Venkatakrishnan","year":"2013","journal-title":"Nature"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"19","author":"RA Friesner","year":"2006","journal-title":"J Med Chem"},{"key":"ref33","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 beta(2) adrenergic receptor revealed by microsecond timescale molecular dynamics","volume":"98","author":"TD Romo","year":"2010","journal-title":"Biophys J"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.drudis.2013.02.007","article-title":"Molecular determinants of drug-receptor binding kinetics","volume":"18","author":"AC Pan","year":"2013","journal-title":"Drug Discov Today"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1152\/physiol.00002.2010","article-title":"Energy landscapes as a tool to integrate GPCR structure, dynamics, and function","volume":"25","author":"X Deupi","year":"2010","journal-title":"Physiology (Bethesda)"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.sbi.2012.03.007","article-title":"Agonist-bound structures of G protein-coupled receptors","volume":"22","author":"G Lebon","year":"2012","journal-title":"Curr Opin Struct Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.bpj.2014.02.002","article-title":"Cholesterol modulates the dimer interface of the beta(2)-adrenergic receptor via cholesterol occupancy sites","volume":"106","author":"X Prasanna","year":"2014","journal-title":"Biophys J"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/978-90-481-8622-8_16","article-title":"Membrane cholesterol in the function and organization of G-protein coupled receptors","volume":"51","author":"YD Paila","year":"2010","journal-title":"Subcell Biochem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.sbi.2011.09.007","article-title":"Uncovering the intimate relationship between lipids, cholesterol and GPCR activation","volume":"21","author":"J Oates","year":"2011","journal-title":"Curr Opin Struct Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1073\/pnas.1215207110","article-title":"Transmembrane helix orientation influences membrane binding of the intracellular juxtamembrane domain in Neu receptor peptides","volume":"110","author":"C Matsushita","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.bpj.2014.06.015","article-title":"Differences in Allosteric Communication Pipelines in the Inactive and Active States of a GPCR","volume":"107","author":"S Bhattacharya","year":"2014","journal-title":"Biophys J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1110\/ps.9.9.1753","article-title":"Modeling of loops in protein structures","volume":"9","author":"A Fiser","year":"2000","journal-title":"Protein Sci"},{"key":"ref43","unstructured":"Accelrys Software Inc., Release 3.5. San Diego."},{"key":"ref44","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s00249-011-0700-9","article-title":"Definition and testing of the GROMOS force-field versions 54A7 and 54B7","volume":"40","author":"N Schmid","year":"2011","journal-title":"Eur Biophys J"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1021\/ct900487a","article-title":"On the validation of molecular dynamics simulations of saturated and cis-monounsaturated phosphatidylcholine lipid bilayers: a comparison with experiment","volume":"6","author":"D Poger","year":"2010","journal-title":"J Chem Theory Comput"},{"key":"ref46","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":"ref47","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","article-title":"GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit","volume":"29","author":"S Pronk","year":"2013","journal-title":"Bioinformatics"},{"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 Essman","year":"1995","journal-title":"J Chem Phys"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"33\u201338","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":"ref50","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1093\/bioinformatics\/btr550","article-title":"MDpocket: open-source cavity detection and characterization on molecular dynamics trajectories","volume":"27","author":"P Schmidtke","year":"2011","journal-title":"Bioinformatics"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S1574-1400(08)00012-1","article-title":"PubChem: Integrated Platform of Small Molecules and Biological Activities. Chapter 12","volume":"4","author":"E Bolton","year":"2008","journal-title":"Ann Rep in Comp Chem"},{"key":"ref52","unstructured":"(2013) Maestro v. New York (New York): Schr\u00f6dinger, LLC."},{"key":"ref53","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-014-9713-7","article-title":"Testing and validation of the Automated Topology Builder (ATB) version 2.0: prediction of hydration free enthalpies","volume":"28","author":"KB Koziara","year":"2014","journal-title":"J Comput Aided Mol Des"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T21:06:22Z","timestamp":1540328782000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004006"}},"subtitle":[],"editor":[{"given":"James M.","family":"Briggs","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2014,12,11]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,12,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004006","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,11]]}}}