{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:19:48Z","timestamp":1767179988504,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009977","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["GM103695"],"award-info":[{"award-number":["GM103695"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["GM65530"],"award-info":[{"award-number":["GM65530"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["GM13656"],"award-info":[{"award-number":["GM13656"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE 1506273"],"award-info":[{"award-number":["CHE 1506273"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The coactivator KIX of CBP uses two binding surfaces to recognize multiple activators and exhibits allostery in ternary complex formation. Activator\u2022coactivator interactions are central to transcriptional regulation, yet the microscopic origins of allostery in dynamic proteins like KIX are largely unknown. Here, we investigate the molecular recognition and allosteric manifestations involved in two KIX ternary systems c-Myb\u2022KIX\u2022MLL and pKID\u2022KIX\u2022MLL. Exploring the hypothesis that binary complex formation prepays an entropic cost for positive cooperativity, we utilize molecular dynamics simulations, side chain methyl order parameters, and differential scanning fluorimetry (DSF) to explore conformational entropy changes in KIX. The protein\u2019s configurational micro-states from structural clustering highlight the utility of protein plasticity in molecular recognition and allostery. We find that apo KIX occupies a wide distribution of lowly-populated configurational states. Each binding partner has its own suite of KIX states that it selects, building a model of molecular recognition fingerprints. Allostery is maximized with MLL pre-binding, which corresponds to the observation of a significant reduction in KIX micro-states observed when MLL binds. With all binding partners, the changes in KIX conformational entropy arise predominantly from changes in the most flexible loop. Likewise, we find that a small molecule and mutations allosterically inhibit\/enhance activator binding by tuning loop dynamics, suggesting that loop-targeting chemical probes could be developed to alter KIX\u2022activator interactions. Experimentally capturing KIX stabilization is challenging, particularly because of the disordered nature of particular activators. However, DSF melting curves allow for inference of relative entropic changes that occur across complexes, which we compare to our computed entropy changes using simulation methyl order parameters.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009977","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T13:34:34Z","timestamp":1650634474000},"page":"e1009977","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Allostery in the dynamic coactivator domain KIX occurs through minor conformational micro-states"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-9458","authenticated-orcid":true,"given":"Amanda L.","family":"Peiffer","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8903-3471","authenticated-orcid":true,"given":"Julie M.","family":"Garlick","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6030-7835","authenticated-orcid":true,"given":"Stephen T.","family":"Joy","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-8327","authenticated-orcid":true,"given":"Anna K.","family":"Mapp","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-5417","authenticated-orcid":true,"given":"Charles L.","family":"Brooks","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"issue":"1","key":"pcbi.1009977.ref001","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.cell.2010.05.039","article-title":"Allostery and Intrinsic Disorder Mediate Transcription Regulation by Conditional Cooperativity","volume":"142","author":"A Garcia-Pino","year":"2010","journal-title":"Cell"},{"issue":"3","key":"pcbi.1009977.ref002","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrm1589","article-title":"Intrinsically unstructured proteins and their functions","volume":"6","author":"HJ Dyson","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"20","key":"pcbi.1009977.ref003","doi-asserted-by":"crossref","first-page":"8311","DOI":"10.1073\/pnas.0700329104","article-title":"Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins","volume":"104","author":"VJ Hilser","year":"2007","journal-title":"Proc Natl Acad Sci"},{"key":"pcbi.1009977.ref004","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1101\/SQB.1961.026.01.048","article-title":"Teleonomic mechanisms in cellular metabolism, growth, and differentiation","volume":"26","author":"J Monod","year":"1961","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"pcbi.1009977.ref005","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1101\/SQB.1961.026.01.037","article-title":"The feedback control mechanisms of biosynthetic L-threonine deaminase by L-isoleucine","volume":"26","author":"JP Changeux","year":"1961","journal-title":"Cold Spring Harb Symp Quant Biol"},{"issue":"1","key":"pcbi.1009977.ref006","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0022-2836(65)80285-6","article-title":"On the nature of allosteric transitions: A plausible model","volume":"12","author":"J Monod","year":"1965","journal-title":"J Mol Biol"},{"issue":"1","key":"pcbi.1009977.ref007","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1146\/annurev.bi.41.070172.004123","article-title":"X-Ray Studies of Protein Mechanisms","volume":"41","author":"RE Dickerson","year":"1972","journal-title":"Annu Rev Biochem"},{"key":"pcbi.1009977.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.biophys.27.1.1","article-title":"The stereochemical mechanism of the cooperative effects in hemoglobin revisited","volume":"27","author":"MF Perutz","year":"1998","journal-title":"Annu Rev Biophys Biomol Struct"},{"issue":"5727","key":"pcbi.1009977.ref009","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1126\/science.1108595","article-title":"Allosteric Mechanisms of Signal Transduction.","volume":"308","author":"J-P Changeux","year":"2005","journal-title":"Science"},{"issue":"11","key":"pcbi.1009977.ref010","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.febslet.2009.03.019","article-title":"The structural basis of allosteric regulation in proteins","volume":"583","author":"RA Laskowski","year":"2009","journal-title":"FEBS Lett"},{"issue":"3","key":"pcbi.1009977.ref011","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1039\/b819720b","article-title":"Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms.","volume":"5","author":"C-J Tsai","year":"2009","journal-title":"Mol Biosyst."},{"issue":"8","key":"pcbi.1009977.ref012","first-page":"1042","article-title":"The origin of allosteric functional modulation: multiple pre-existing pathways.","volume":"17","author":"A del Sol","year":"2009","journal-title":"Struct Lond Engl 1993."},{"issue":"1","key":"pcbi.1009977.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jmb.2008.02.034","article-title":"Allostery: absence of a change in shape does not imply that allostery is not at play","volume":"378","author":"C-J Tsai","year":"2008","journal-title":"J Mol Biol"},{"issue":"2","key":"pcbi.1009977.ref014","doi-asserted-by":"crossref","first-page":"e1003394","DOI":"10.1371\/journal.pcbi.1003394","article-title":"A Unified View of \u201cHow Allostery Works.\u201d","volume":"10","author":"C-J Tsai","year":"2014","journal-title":"PLOS Comput Biol."},{"issue":"24","key":"pcbi.1009977.ref015","doi-asserted-by":"crossref","first-page":"8458","DOI":"10.1073\/pnas.82.24.8458","article-title":"Active site dynamics of ribonuclease","volume":"82","author":"AT Br\u00fcnger","year":"1985","journal-title":"Proc Natl Acad Sci"},{"issue":"2","key":"pcbi.1009977.ref016","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1021\/ja9913838","article-title":"Protein Dynamics in Enzymatic Catalysis: Exploration of Dihydrofolate Reductase","volume":"122","author":"JL Radkiewicz","year":"2000","journal-title":"J Am Chem Soc"},{"issue":"1","key":"pcbi.1009977.ref017","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1146\/annurev-biophys-050511-102319","article-title":"Structural and Energetic Basis of Allostery.","volume":"41","author":"VJ Hilser","year":"2012","journal-title":"Annu Rev Biophys."},{"issue":"11","key":"pcbi.1009977.ref018","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1073\/pnas.1120519109","article-title":"Agonism\/antagonism switching in allosteric ensembles","volume":"109","author":"HN Motlagh","year":"2012","journal-title":"Proc Natl Acad Sci"},{"issue":"37","key":"pcbi.1009977.ref019","doi-asserted-by":"crossref","first-page":"13722","DOI":"10.1073\/pnas.0603282103","article-title":"Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics","volume":"103","author":"J Zimmermann","year":"2006","journal-title":"Proc Natl Acad Sci"},{"issue":"13","key":"pcbi.1009977.ref020","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1101\/gad.14.13.1553","article-title":"CBP\/p300 in cell growth, transformation, and development","volume":"14","author":"RH Goodman","year":"2000","journal-title":"Genes Dev"},{"issue":"4","key":"pcbi.1009977.ref021","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1093\/nar\/gkt1147","article-title":"Molecular recognition by the KIX domain and its role in gene regulation","volume":"42","author":"JK Thakur","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pcbi.1009977.ref022","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1006\/jmbi.1999.2658","article-title":"Structural analyses of CREB-CBP transcriptional activator-coactivator complexes by NMR spectroscopy: implications for mapping the boundaries of structural domains11Edited by F. E. Cohen","volume":"287","author":"I Radhakrishnan","year":"1999","journal-title":"J Mol Biol"},{"issue":"45","key":"pcbi.1009977.ref023","doi-asserted-by":"crossref","first-page":"43168","DOI":"10.1074\/jbc.M207660200","article-title":"Cooperativity in Transcription Factor Binding to the Coactivator CREB-binding Protein (CBP) THE MIXED LINEAGE LEUKEMIA PROTEIN (MLL) ACTIVATION DOMAIN BINDS TO AN ALLOSTERIC SITE ON THE KIX DOMAIN.","volume":"277","author":"NK Goto","year":"2002","journal-title":"J Biol Chem"},{"issue":"47","key":"pcbi.1009977.ref024","doi-asserted-by":"crossref","first-page":"13956","DOI":"10.1021\/bi026222m","article-title":"Structurally Distinct Modes of Recognition of the KIX Domain of CBP by Jun and CREB","volume":"41","author":"KM Campbell","year":"2002","journal-title":"Biochemistry"},{"issue":"43","key":"pcbi.1009977.ref025","doi-asserted-by":"crossref","first-page":"12481","DOI":"10.1021\/bi0353023","article-title":"KIX-Mediated Assembly of the CBP\u2212CREB\u2212HTLV-1 Tax Coactivator\u2212Activator Complex.","volume":"42","author":"AC Vendel","year":"2003","journal-title":"Biochemistry"},{"issue":"3","key":"pcbi.1009977.ref026","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jmb.2004.01.038","article-title":"Solution Structure of the KIX Domain of CBP Bound to the Transactivation Domain of c-Myb","volume":"337","author":"T Zor","year":"2004","journal-title":"J Mol Biol"},{"issue":"4","key":"pcbi.1009977.ref027","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1021\/bi035612l","article-title":"NMR Mapping of the HIV-1 Tat Interaction Surface of the KIX Domain of the Human Coactivator CBP","volume":"43","author":"AC Vendel","year":"2004","journal-title":"Biochemistry"},{"issue":"2","key":"pcbi.1009977.ref028","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1172\/JCI38030","article-title":"c-Myb binds MLL through menin in human leukemia cells and is an important driver of MLL-associated leukemogenesis","volume":"120","author":"S Jin","year":"2010","journal-title":"J Clin Invest"},{"issue":"1","key":"pcbi.1009977.ref029","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1182\/blood-2005-12-5014","article-title":"c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells","volume":"108","author":"JL Hess","year":"2006","journal-title":"Blood"},{"issue":"2","key":"pcbi.1009977.ref030","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0959-437X(05)80281-3","article-title":"Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells","volume":"2","author":"T. Graf","year":"1992","journal-title":"Curr Opin Genet Dev"},{"issue":"12","key":"pcbi.1009977.ref031","doi-asserted-by":"crossref","first-page":"e82684","DOI":"10.1371\/journal.pone.0082684","article-title":"Genetic interaction between mutations in c-Myb and the KIX domains of CBP and p300 affects multiple blood cell lineages and influences both gene activation and repression","volume":"8","author":"LH Kasper","year":"2013","journal-title":"PloS One"},{"issue":"5","key":"pcbi.1009977.ref032","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.jmb.2005.09.059","article-title":"Structural Basis for Cooperative Transcription Factor Binding to the CBP Coactivator","volume":"355","author":"RN De Guzman","year":"2006","journal-title":"J Mol Biol"},{"issue":"7","key":"pcbi.1009977.ref033","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1021\/cb4002188","article-title":"Allosteric Communication in the KIX Domain Proceeds through Dynamic Repacking of the Hydrophobic Core.","volume":"8","author":"S Br\u00fcschweiler","year":"2013","journal-title":"ACS Chem Biol"},{"issue":"33","key":"pcbi.1009977.ref034","doi-asserted-by":"crossref","first-page":"12061","DOI":"10.1073\/pnas.1406033111","article-title":"Dissecting allosteric effects of activator\u2013coactivator complexes using a covalent small molecule ligand","volume":"111","author":"N Wang","year":"2014","journal-title":"Proc Natl Acad Sci"},{"issue":"9","key":"pcbi.1009977.ref035","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1021\/ja3122334","article-title":"Ordering a Dynamic Protein Via a Small-Molecule Stabilizer","volume":"135","author":"N Wang","year":"2013","journal-title":"J Am Chem Soc"},{"issue":"33","key":"pcbi.1009977.ref036","doi-asserted-by":"crossref","first-page":"12067","DOI":"10.1073\/pnas.1405831111","article-title":"Prepaying the entropic cost for allosteric regulation in KIX","volume":"111","author":"SM Law","year":"2014","journal-title":"Proc Natl Acad Sci"},{"issue":"35","key":"pcbi.1009977.ref037","doi-asserted-by":"crossref","first-page":"14237","DOI":"10.1073\/pnas.1313548110","article-title":"The allosteric communication pathways in KIX domain of CBP","volume":"110","author":"F Palazzesi","year":"2013","journal-title":"Proc Natl Acad Sci"},{"issue":"8","key":"pcbi.1009977.ref038","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1021\/ja809947w","article-title":"Direct observation of the dynamic process underlying allosteric signal transmission","volume":"131","author":"S Br\u00fcschweiler","year":"2009","journal-title":"J Am Chem Soc"},{"issue":"9","key":"pcbi.1009977.ref039","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1038\/nprot.2007.321","article-title":"The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability.","volume":"2","author":"FH Niesen","year":"2007","journal-title":"Nat Protoc."},{"issue":"1","key":"pcbi.1009977.ref040","doi-asserted-by":"crossref","first-page":"28.9.1","DOI":"10.1002\/0471140864.ps2809s79","article-title":"Analysis of Protein Stability and Ligand Interactions by Thermal Shift Assay.","volume":"79","author":"K Huynh","year":"2015","journal-title":"Curr Protoc Protein Sci"},{"key":"pcbi.1009977.ref041","doi-asserted-by":"crossref","DOI":"10.1021\/acs.jpclett.6b02894","volume-title":"Extraction of Thermodynamic Parameters of Protein Unfolding Using Parallelized Differential Scanning Fluorimetry","author":"TA Wright","year":"2017"},{"issue":"19","key":"pcbi.1009977.ref042","doi-asserted-by":"crossref","first-page":"5963","DOI":"10.1021\/acs.jpclett.9b02226","article-title":"Enhanced Sampling Applied to Modeling Allosteric Regulation in Transcription","volume":"10","author":"Y Wang","year":"2019","journal-title":"J Phys Chem Lett"},{"issue":"12","key":"pcbi.1009977.ref043","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1002\/pro.5560051228","article-title":"Insights into the local residual entropy of proteins provided by NMR relaxation","volume":"5","author":"Z Li","year":"1996","journal-title":"Protein Sci"},{"issue":"46","key":"pcbi.1009977.ref044","doi-asserted-by":"crossref","first-page":"13814","DOI":"10.1021\/bi026380d","article-title":"Temperature dependence of the internal dynamics of a calmodulin-peptide complex","volume":"41","author":"AL Lee","year":"2002","journal-title":"Biochemistry"},{"issue":"40","key":"pcbi.1009977.ref045","doi-asserted-by":"crossref","first-page":"15092","DOI":"10.1021\/ja405200u","article-title":"Microscopic Insights into the NMR Relaxation-Based Protein Conformational Entropy Meter","volume":"135","author":"V Kasinath","year":"2013","journal-title":"J Am Chem Soc"},{"issue":"5","key":"pcbi.1009977.ref046","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/prot.24789","article-title":"On the relationship between NMR-derived amide order parameters and protein backbone entropy changes","volume":"83","author":"KA Sharp","year":"2015","journal-title":"Proteins"},{"issue":"8","key":"pcbi.1009977.ref047","doi-asserted-by":"crossref","first-page":"5601","DOI":"10.1128\/MCB.19.8.5601","article-title":"Role of Secondary Structure in Discrimination between Constitutive and Inducible Activators","volume":"19","author":"D Parker","year":"1999","journal-title":"Mol Cell Biol"},{"issue":"3","key":"pcbi.1009977.ref048","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0014-5793(98)00680-2","article-title":"Conformational preferences in the Ser133-phosphorylated and non-phosphorylated forms of the kinase inducible transactivation domain of CREB","volume":"430","author":"I Radhakrishnan","year":"1998","journal-title":"FEBS Lett"},{"issue":"44","key":"pcbi.1009977.ref049","doi-asserted-by":"crossref","first-page":"42241","DOI":"10.1074\/jbc.M207361200","article-title":"Roles of Phosphorylation and Helix Propensity in the Binding of the KIX Domain of CREB-binding Protein by Constitutive (c-Myb) and Inducible (CREB) Activators.","volume":"277","author":"T Zor","year":"2002","journal-title":"J Biol Chem"},{"issue":"3","key":"pcbi.1009977.ref050","doi-asserted-by":"crossref","first-page":"e1002420","DOI":"10.1371\/journal.pcbi.1002420","article-title":"Conformational Control of the Binding of the Transactivation Domain of the MLL Protein and c-Myb to the KIX Domain of CREB.","volume":"8","author":"EN Korkmaz","year":"2012","journal-title":"PLOS Comput Biol."},{"issue":"2","key":"pcbi.1009977.ref051","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jcc.540040211","article-title":"CHARMM: A program for macromolecular energy, minimization, and dynamics calculations","volume":"4","author":"BR Brooks","year":"1983","journal-title":"J Comput Chem"},{"issue":"10","key":"pcbi.1009977.ref052","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1002\/jcc.21287","article-title":"CHARMM: the biomolecular simulation program","volume":"30","author":"BR Brooks","year":"2009","journal-title":"J Comput Chem"},{"issue":"7","key":"pcbi.1009977.ref053","doi-asserted-by":"crossref","first-page":"e1005659","DOI":"10.1371\/journal.pcbi.1005659","article-title":"OpenMM 7: Rapid development of high performance algorithms for molecular dynamics","volume":"13","author":"P Eastman","year":"2017","journal-title":"PLOS Comput Biol"},{"issue":"5","key":"pcbi.1009977.ref054","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jmgm.2003.12.005","article-title":"MMTSB Tool Set: enhanced sampling and multiscale modeling methods for applications in structural biology","volume":"22","author":"M Feig","year":"2004","journal-title":"J Mol Graph Model"},{"issue":"5","key":"pcbi.1009977.ref055","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nchembio.347","article-title":"The role of conformational entropy in molecular recognition by calmodulin","volume":"6","author":"MS Marlow","year":"2010","journal-title":"Nat Chem Biol"},{"issue":"1","key":"pcbi.1009977.ref056","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.sbi.2012.11.005","article-title":"The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation","volume":"23","author":"AJ Wand","year":"2013","journal-title":"Curr Opin Struct Biol"},{"issue":"5","key":"pcbi.1009977.ref057","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1021\/cr040422h","article-title":"Characterization of the Fast Dynamics of Protein Amino Acid Side Chains Using NMR Relaxation in Solution","volume":"106","author":"TI Igumenova","year":"2006","journal-title":"Chem Rev"},{"issue":"17","key":"pcbi.1009977.ref058","doi-asserted-by":"crossref","first-page":"4546","DOI":"10.1021\/ja00381a009","article-title":"Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity","volume":"104","author":"G Lipari","year":"1982","journal-title":"J Am Chem Soc"},{"issue":"5","key":"pcbi.1009977.ref059","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1021\/cb900028j","article-title":"Amphipathic Small Molecules Mimic the Binding Mode and Function of Endogenous Transcription Factors.","volume":"4","author":"SJ Buhrlage","year":"2009","journal-title":"ACS Chem Biol"},{"issue":"8","key":"pcbi.1009977.ref060","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1021\/cb3002733","article-title":"Profiling the Dynamic Interfaces of Fluorinated Transcription Complexes for Ligand Discovery and Characterization.","volume":"7","author":"WC Pomerantz","year":"2012","journal-title":"ACS Chem Biol"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1009977","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009977","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T22:37:17Z","timestamp":1675377437000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009977"}},"subtitle":[],"editor":[{"given":"Rebecca C.","family":"Wade","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,4,22]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1009977","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,22]]}}}