{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:32:33Z","timestamp":1768519953720,"version":"3.49.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T00:00:00Z","timestamp":1464825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education\u2014Singapore","doi-asserted-by":"publisher","award":["MOE2012-T3-1-008"],"award-info":[{"award-number":["MOE2012-T3-1-008"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1004840","type":"journal-article","created":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T13:32:44Z","timestamp":1464874364000},"page":"e1004840","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Predicting Allosteric Effects from Orthosteric Binding in Hsp90-Ligand Interactions: Implications for Fragment-Based Drug Design"],"prefix":"10.1371","volume":"12","author":[{"given":"Arun","family":"Chandramohan","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4175-5886","authenticated-orcid":true,"given":"Srinath","family":"Krishnamurthy","sequence":"additional","affiliation":[]},{"given":"Andreas","family":"Larsson","sequence":"additional","affiliation":[]},{"given":"Paer","family":"Nordlund","sequence":"additional","affiliation":[]},{"given":"Anna","family":"Jansson","sequence":"additional","affiliation":[]},{"given":"Ganesh S.","family":"Anand","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2016,6,2]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nchembio.232","article-title":"The role of dynamic conformational ensembles in biomolecular recognition","volume":"5","author":"DD Boehr","year":"2009","journal-title":"Nat Chem Biol"},{"key":"ref2","first-page":"256","volume":"xx","author":"K Johnson","year":"2003"},{"issue":"5","key":"ref3","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.tips.2014.03.006","article-title":"Unraveling structural mechanisms of allosteric drug action","volume":"35","author":"R Nussinov","year":"2014","journal-title":"Trends in pharmacological sciences"},{"issue":"8","key":"ref4","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1110\/ps.03259908","article-title":"Allostery and cooperativity revisited","volume":"17","author":"Q Cui","year":"2008","journal-title":"Protein Sci"},{"issue":"7496","key":"ref5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nature13001","article-title":"The ensemble nature of allostery","volume":"508","author":"HN Motlagh","year":"2014","journal-title":"Nature"},{"issue":"22","key":"ref6","doi-asserted-by":"crossref","first-page":"12570","DOI":"10.1073\/pnas.2135471100","article-title":"Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins","volume":"100","author":"O Miyashita","year":"2003","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"32","key":"ref7","doi-asserted-by":"crossref","first-page":"11182","DOI":"10.1073\/pnas.0802524105","article-title":"Dynamic energy landscape view of coupled binding and protein conformational change: induced-fit versus population-shift mechanisms","volume":"105","author":"K Okazaki","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"8","key":"ref8","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1111\/febs.12707","article-title":"Dynamic protein ligand interactions\u2014insights from MS","volume":"281","author":"C Schmidt","year":"2014","journal-title":"The FEBS journal"},{"issue":"11","key":"ref9","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1039\/c2cs35035a","article-title":"Mass spectrometry based tools to investigate protein-ligand interactions for drug discovery","volume":"41","author":"KJ Pacholarz","year":"2012","journal-title":"Chemical Society reviews"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1017\/S0033583500005217","article-title":"Hydrogen exchange and structural dynamics of proteins and nucleic acids","volume":"16","author":"SW Englander","year":"1983","journal-title":"Q Rev Biophys"},{"issue":"3","key":"ref11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF00421225","article-title":"Hydrogen exchange and the dynamic structure of proteins","volume":"48","author":"C Woodward","year":"1982","journal-title":"Mol Cell Biochem"},{"issue":"14","key":"ref12","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/ac9601526","article-title":"Mass spectrometric determination of isotopic exchange rates of amide hydrogens located on the surfaces of proteins","volume":"68","author":"K Dharmasiri","year":"1996","journal-title":"Anal. Chem"},{"issue":"23","key":"ref13","doi-asserted-by":"crossref","first-page":"13264","DOI":"10.1073\/pnas.2232255100","article-title":"Identification of the protein kinase A regulatory RIalpha-catalytic subunit interface by amide H\/2H exchange and protein docking","volume":"100","author":"GS Anand","year":"2003","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"ref14","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1006\/jmbi.2000.4416","article-title":"Solvent accessibility of the thrombin-thrombomodulin interface","volume":"306","author":"JG Mandell","year":"2001","journal-title":"Journal of Molecular Biology"},{"issue":"25","key":"ref15","doi-asserted-by":"crossref","first-page":"14705","DOI":"10.1073\/pnas.95.25.14705","article-title":"Identification of protein-protein interfaces by decreased amide proton solvent accessibility","volume":"95","author":"JG Mandell","year":"1998","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"19","key":"ref16","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1021\/ac980553g","article-title":"Measurement of amide hydrogen exchange by MALDI-TOF mass spectrometry","volume":"70","author":"JG Mandell","year":"1998","journal-title":"Anal. Chem"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","DOI":"10.1074\/mcp.M110.004390","article-title":"Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation: conformational selection highlights a new concept in allosteric inhibitor design","volume":"10","author":"S Badireddy","year":"2011","journal-title":"Mol. Cell Proteomics"},{"issue":"15","key":"ref18","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1016\/j.bmcl.2014.05.070","article-title":"HDX reveals unique fragment ligands for the vitamin D receptor","volume":"24","author":"MW Carson","year":"2014","journal-title":"Bioorganic & medicinal chemistry letters"},{"issue":"3","key":"ref19","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nrd2220","article-title":"A decade of fragment-based drug design: strategic advances and lessons learned","volume":"6","author":"PJ Hajduk","year":"2007","journal-title":"Nature reviews Drug discovery"},{"issue":"4","key":"ref20","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.cbpa.2011.06.008","article-title":"Efficiency of hit generation and structural characterization in fragment-based ligand discovery","volume":"15","author":"A Larsson","year":"2011","journal-title":"Current opinion in chemical biology"},{"issue":"19","key":"ref21","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/S1359-6446(03)02831-9","article-title":"A 'rule of three' for fragment-based lead discovery?","volume":"8","author":"M Congreve","year":"2003","journal-title":"Drug Discov Today"},{"issue":"14","key":"ref22","doi-asserted-by":"crossref","first-page":"5363","DOI":"10.1021\/ja110571r","article-title":"Fragment growing induces conformational changes in acetylcholine-binding protein: a structural and thermodynamic analysis","volume":"133","author":"E Edink","year":"2011","journal-title":"Journal of the American Chemical Society"},{"issue":"5","key":"ref23","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.tips.2012.02.006","article-title":"Experiences in fragment-based drug discovery","volume":"33","author":"CW Murray","year":"2012","journal-title":"Trends in pharmacological sciences"},{"issue":"25","key":"ref24","doi-asserted-by":"crossref","first-page":"14536","DOI":"10.1073\/pnas.93.25.14536","article-title":"Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90","volume":"93","author":"C Schneider","year":"1996","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"11","key":"ref25","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.2174\/156802606777812068","article-title":"Hsp90: a novel target for cancer therapy","volume":"6","author":"DB Solit","year":"2006","journal-title":"Current topics in medicinal chemistry"},{"issue":"16","key":"ref26","doi-asserted-by":"crossref","first-page":"5942","DOI":"10.1021\/jm100059d","article-title":"Fragment-based drug discovery applied to Hsp90. Discovery of two lead series with high ligand efficiency","volume":"53","author":"CW Murray","year":"2010","journal-title":"Journal of medicinal chemistry"},{"issue":"15","key":"ref27","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.1021\/jm900357y","article-title":"Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone","volume":"52","author":"PA Brough","year":"2009","journal-title":"Journal of medicinal chemistry"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1747-0285.2007.00535.x","article-title":"Discovery and design of novel HSP90 inhibitors using multiple fragment-based design strategies","volume":"70","author":"JR Huth","year":"2007","journal-title":"Chemical biology & drug design"},{"issue":"6","key":"ref29","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.bpj.2014.07.050","article-title":"Active site coupling in PDE:PKA complexes promotes resetting of mammalian cAMP signaling","volume":"107","author":"S Krishnamurthy","year":"2014","journal-title":"Biophysical journal"},{"issue":"7","key":"ref30","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1177\/1087057112445785","article-title":"Fragment screening using capillary electrophoresis (CEfrag) for hit identification of heat shock protein 90 ATPase inhibitors","volume":"17","author":"C Austin","year":"2012","journal-title":"J Biomol Screen"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0092-8674(00)80203-2","article-title":"Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent","volume":"89","author":"CE Stebbins","year":"1997","journal-title":"Cell"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0092-8674(00)80314-1","article-title":"Identification and structural characterization of the ATP\/ADP-binding site in the Hsp90 molecular chaperone","volume":"90","author":"C Prodromou","year":"1997","journal-title":"Cell"},{"issue":"7087","key":"ref33","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/nature04716","article-title":"Crystal structure of an Hsp90-nucleotide-p23\/Sba1 closed chaperone complex","volume":"440","author":"MM Ali","year":"2006","journal-title":"Nature"},{"issue":"12","key":"ref34","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1021\/jm200350g","article-title":"How well can fragments explore accessed chemical space? A case study from heat shock protein 90","volume":"54","author":"SD Roughley","year":"2011","journal-title":"Journal of medicinal chemistry"},{"issue":"1","key":"ref35","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0003-2697(03)00060-5","article-title":"Filter binding assay for the geldanamycin-heat shock protein 90 interaction","volume":"317","author":"CW Carreras","year":"2003","journal-title":"Anal. Biochem"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0022-2836(02)00919-1","article-title":"Amide H\/2H exchange reveals communication between the cAMP and catalytic subunit-binding sites in the R(I)alpha subunit of protein kinase A","volume":"323","author":"GS Anand","year":"2002","journal-title":"Journal of Molecular Biology"},{"issue":"2","key":"ref37","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.str.2013.11.007","article-title":"Architecture of a dsDNA viral capsid in complex with its maturation protease","volume":"22","author":"D Veesler","year":"2014","journal-title":"Structure"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"e959816","DOI":"10.4161\/21597073.2014.959816","article-title":"Distinguishing direct binding interactions from allosteric effects in the protease-HK97 prohead I \u03b4 domain complex by amide H\/D exchange mass spectrometry","volume":"4","author":"S Krishnamurthy","year":"2014","journal-title":"Bacteriophage"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T04:19:29Z","timestamp":1540268369000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004840"}},"subtitle":[],"editor":[{"given":"Jin","family":"Liu","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2016,6,2]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004840","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,2]]}}}