{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:23:46Z","timestamp":1781537026393,"version":"3.54.5"},"reference-count":59,"publisher":"Impact Journals, LLC","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncotarget"],"published-print":{"date-parts":[[2018,3,2]]},"DOI":"10.18632\/oncotarget.24459","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T06:48:15Z","timestamp":1518158895000},"page":"13713-13732","source":"Crossref","is-referenced-by-count":29,"title":["Computational modeling suggests impaired interactions between NKX2.5 and GATA4 in individuals carrying a novel pathogenic D16N NKX2.5 mutation"],"prefix":"10.18632","volume":"9","author":[{"given":"Saidulu","family":"Mattapally","sequence":"first","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrityunjay","family":"Singh","sequence":"additional","affiliation":[{"name":"Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kona Samba","family":"Murthy","sequence":"additional","affiliation":[{"name":"Innova Children\u2019s Heart Hospital, Tarnaka, Hyderabad 500017, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailendra","family":"Asthana","sequence":"additional","affiliation":[{"name":"Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay K.","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India"},{"name":"Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7892","published-online":{"date-parts":[[2018,2,9]]},"reference":[{"key":"1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1006\/geno.1995.1027","article-title":"Assignment of cardiac homeobox gene CSX to human chromosome 5q34","volume":"27","author":"Yazaki","year":"1995","journal-title":"Genomics"},{"key":"2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1006\/dbio.1996.0212","article-title":"NK-2 homeobox genes and heart development","volume":"178","author":"Harvey","year":"1996","journal-title":"Dev Biol"},{"key":"3","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1074\/jbc.273.5.2917","article-title":"A novel nk-2-related transcription factor associated with human fetal liver and hepatocellular carcinoma","volume":"273","author":"Locker","year":"1998","journal-title":"J Biol Chem"},{"key":"4","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/90123","article-title":"Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation","volume":"28","author":"Komuro","year":"2001","journal-title":"Nat Genet"},{"key":"5","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1093\/emboj\/16.18.5687","article-title":"The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors","volume":"16","author":"Nemer","year":"1997","journal-title":"EMBO J"},{"key":"6","doi-asserted-by":"crossref","first-page":"6312","DOI":"10.1021\/bi300849c","article-title":"Crystal structure of the human NKX2. 5 homeodomain in complex with DNA target","volume":"51","author":"Nam","year":"2012","journal-title":"Biochemistry"},{"key":"7","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1242\/dev.126.6.1269","article-title":"The cardiac homeobox gene Csx\/Nkx2.5 lies genetically upstream of multiple genes essential for heart development","volume":"126","author":"Izumo","year":"1999","journal-title":"Development"},{"key":"8","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1101\/gad.9.13.1654","article-title":"Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5","volume":"9","author":"Harvey","year":"1995","journal-title":"Genes Dev"},{"key":"9","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1242\/dev.095562","article-title":"Nkx genes are essential for maintenance of ventricular identity","volume":"140","author":"Yelon","year":"2013","journal-title":"Development"},{"key":"10","first-page":"577","article-title":"Human Gene Mutation Database (HGMD): 2003 update","volume":"21","author":"Cooper","year":"2003","journal-title":"Hum Mutat"},{"key":"11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10528-016-9780-7","article-title":"Genetics of Congenital Heart Disease: Past and Present","volume":"55","author":"Benedek","year":"2017","journal-title":"Biochem Genet"},{"key":"12","doi-asserted-by":"crossref","first-page":"e83295","DOI":"10.1371\/journal.pone.0083295","article-title":"Transcriptional defect of an inherited NKX2-5 haplotype comprising a SNP, a nonsynonymous and a synonymous mutation, associated with human congenital heart disease","volume":"8","author":"Borlak","year":"2013","journal-title":"PLoS One"},{"key":"13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3390\/genes7020006","article-title":"Genetics of congenital heart defects: the NKX2-5 gene, a key player","volume":"7","author":"Rajakumar","year":"2016","journal-title":"Genes"},{"key":"14","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1161\/CIRCULATIONAHA.106.183056","article-title":"Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics","volume":"115","author":"Webb","year":"2007","journal-title":"Circulation"},{"key":"15","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1161\/CIRCULATIONAHA.106.183216","article-title":"Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics","volume":"115","author":"Webb","year":"2007","journal-title":"Circulation"},{"key":"16","first-page":"e21","article-title":"American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics\u20142009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee","volume":"119","author":"Ho","year":"2009","journal-title":"Circulation"},{"key":"17","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1161\/CIRCULATIONAHA.106.618124","article-title":"Ventricular septal defects","volume":"114","author":"Sahn","year":"2006","journal-title":"Circulation"},{"key":"18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.4103\/0971-6866.73412","article-title":"Congenital malformations at birth in Central India: A rural medical college hospital based data","volume":"16","author":"Jain","year":"2010","journal-title":"Indian J Hum Genet"},{"key":"19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12881-015-0152-7","article-title":"c. 620C> T mutation in GATA4 is associated with congenital heart disease in South India","volume":"16","author":"Banerjee","year":"2015","journal-title":"BMC Med Genet"},{"key":"20","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1021\/acs.biochem.6b00171","article-title":"Intermolecular Interactions of Cardiac Transcription Factors NKX2.5 and TBX5","volume":"55","author":"Nam","year":"2016","journal-title":"Biochemistry"},{"key":"21","doi-asserted-by":"crossref","first-page":"D142","DOI":"10.1093\/nar\/gkt997","article-title":"JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles","volume":"42","author":"Tan","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"22","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jmb.2004.02.002","article-title":"Prediction and functional analysis of native disorder in proteins from the three kingdoms of life","volume":"337","author":"Jones","year":"2004","journal-title":"J Mol Biol"},{"key":"23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1472-6807-7-9","article-title":"Evaluation of the structural quality of modeled proteins by using globularity criteria","volume":"7","author":"Colonna","year":"2007","journal-title":"BMC Struct Biol"},{"key":"24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature13999","article-title":"Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch","volume":"519","author":"Forman-Kay","year":"2015","journal-title":"Nature"},{"key":"25","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2016.01.004","article-title":"Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis","volume":"164","author":"Pollard","year":"2016","journal-title":"Cell"},{"key":"26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrm3920","article-title":"Intrinsically disordered proteins in cellular signalling and regulation","volume":"16","author":"Dyson","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"key":"27","doi-asserted-by":"crossref","first-page":"e1000376","DOI":"10.1371\/journal.pcbi.1000376","article-title":"Prediction of protein binding regions in disordered proteins","volume":"5","author":"Dosztanyi","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"28","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program to check the stereochemical quality of protein structures","volume":"26","author":"Thornton","year":"1993","journal-title":"J Appl Cryst"},{"key":"29","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00894-009-0454-9","article-title":"Solvent accessible surface area approximations for rapid and accurate protein structure prediction","volume":"15","author":"Meiler","year":"2009","journal-title":"J Mol Model"},{"key":"30","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0959-440X(94)90172-4","article-title":"Knowledge-based validation of protein structure coordinates derived by X-ray crystallography and NMR spectroscopy","volume":"4","author":"Thornton","year":"1994","journal-title":"Curr Opin Struct Biol"},{"key":"31","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Sippl","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"32","first-page":"1","article-title":"Protein structure modeling with MODELLER","author":"Sali","year":"2014","journal-title":"Protein Structure Prediction"},{"key":"33","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1093\/bioinformatics\/bth195","article-title":"The DISOPRED server for the prediction of protein disorder","volume":"20","author":"Jones","year":"2004","journal-title":"Bioinformatics"},{"key":"34","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btp518","article-title":"ANCHOR: web server for predicting protein binding regions in disordered proteins","volume":"25","author":"Simon","year":"2009","journal-title":"Bioinformatics"},{"key":"35","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1093\/nar\/gkg545","article-title":"ELM server: A new resource for investigating short functional sites in modular eukaryotic proteins","volume":"31","author":"Via","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"36","unstructured":"Discovery Informatics Suite 2016-3. New York (NY), Schr\u00f6dinger, LLC. 2016."},{"key":"37","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1021\/bi400107h","article-title":"Different molecular mechanisms of inhibition of bovine viral diarrhea virus and hepatitis C virus RNA-dependent RNA polymerases by a novel benzimidazole","volume":"52","author":"La Colla","year":"2013","journal-title":"Biochemistry"},{"key":"38","doi-asserted-by":"crossref","first-page":"D190","DOI":"10.1093\/nar\/gkm895","article-title":"The universal protein resource (UniProt)","volume":"36","author":"Consortium U, and UniProt Consortium","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"39","doi-asserted-by":"crossref","first-page":"W480","DOI":"10.1093\/nar\/gkq471","article-title":"DrugScorePPI webserver: fast and accurate in silico alanine scanning for scoring protein-protein interactions","volume":"38","author":"Gohlke","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"40","unstructured":"Biologics Suite 2017-2: BioLuminate, Schr\u00f6dinger, LLC, New York, NY. 2017."},{"key":"41","doi-asserted-by":"crossref","first-page":"W333","DOI":"10.1093\/nar\/gkt450","article-title":"BeAtMuSiC: prediction of changes in protein-protein binding affinity on mutations","volume":"41","author":"Gilis","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"42","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1016\/j.celrep.2014.07.055","article-title":"Intrinsically disordered segments affect protein half-life in the cell and during evolution","volume":"8","author":"Babu","year":"2014","journal-title":"Cell Rep"},{"key":"43","doi-asserted-by":"crossref","first-page":"D512","DOI":"10.1093\/nar\/gku1267","article-title":"PhosphoSitePlus, 2014: mutations, PTMs and recalibrations","volume":"43","author":"Skrzypek","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"44","first-page":"bat038","article-title":"Construction of protein phosphorylation networks by data mining, text mining and ontology integration: analysis of the spindle checkpoint","volume":"2013","author":"Wu","year":"2013","journal-title":"Database (Oxford)"},{"key":"45","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.sbi.2011.03.011","article-title":"Intrinsically disordered proteins: regulation and disease","volume":"21","author":"Gsponer","year":"2011","journal-title":"Curr Opin Struct Biol"},{"key":"46","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrm3920","article-title":"Intrinsically disordered proteins in cellular signalling and regulation","volume":"16","author":"Dyson","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"key":"47","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.cell.2013.02.014","article-title":"Transcriptional regulation and its misregulation in disease","volume":"152","author":"Young","year":"2013","journal-title":"Cell"},{"key":"48","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.str.2011.09.021","article-title":"Phosphorylation in Protein-Protein Binding: Effect on Stability and Function","volume":"19","author":"Panchenko","year":"2011","journal-title":"Structure"},{"key":"49","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1039\/c3mb25514j","article-title":"Regulation of protein-protein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes","volume":"9","author":"Panchenko","year":"2013","journal-title":"Mol Biosyst"},{"key":"50","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/joa.12486","article-title":"Cardiac troponin T is necessary for normal development in the embryonic chick heart","volume":"229","author":"Loughna","year":"2016","journal-title":"J Anat"},{"key":"51","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.yjmcc.2013.05.020","article-title":"Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4","volume":"62","author":"Lee","year":"2013","journal-title":"J Mol Cell Cardiol"},{"key":"52","volume-title":"Molecular cloning: A laboratory manual","author":"Maniatis","year":"1989","edition":"2nd ed."},{"key":"53","article-title":"Multiple sequence alignment using ClustalW and ClustalX","author":"Higgins","year":"2002","journal-title":"Curr Protoc Bioinformatics"},{"key":"54","unstructured":"Schr\u00f6dinger Release 2017-2: Desmond Molecular Dynamics System, D. E. Shaw Research, New York, NY, 2017. Maestro-Desmond Interoperability Tools, Schr\u00f6dinger, New York, NY, 2017."},{"key":"55","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.1063\/1.1808117","article-title":"A modified TIP3P water potential for simulation with Ewald summation","volume":"121","author":"Brooks","year":"2004","journal-title":"J Chem Phys"},{"key":"56","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.1038\/s41598-017-05314-z","article-title":"A novel STK1-targeted small-molecule as an \u201cantibiotic resistance breaker\u201d against multidrug-resistant Staphylococcus aureus","volume":"7","author":"Pancholi","year":"2017","journal-title":"Sci Rep"},{"key":"57","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1063\/1.449071","article-title":"The nose-hoover thermostat","volume":"83","author":"Holian","year":"1985","journal-title":"J Chem Phys"},{"key":"58","first-page":"3234","article-title":"Remarks on \u201cConstant-temperature molecular dynamics with momentum conservation\u201d","volume":"50","author":"Martyna","year":"1994","journal-title":"Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics"},{"key":"59","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1016\/S0969-2126(99)80033-1","article-title":"New tricks for modelers from the crystallography toolkit: the particle mesh Ewald algorithm and its use in nucleic acid simulations","volume":"7","author":"Pedersen","year":"1999","journal-title":"Structure"}],"container-title":["Oncotarget"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.24459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,14]],"date-time":"2022-08-14T03:29:02Z","timestamp":1660447742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.24459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,9]]},"references-count":59,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2018,3,2]]}},"alternative-id":["24459","29568389"],"URL":"https:\/\/doi.org\/10.18632\/oncotarget.24459","relation":{},"ISSN":["1949-2553"],"issn-type":[{"value":"1949-2553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,9]]}}}