{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:19:00Z","timestamp":1779193140235,"version":"3.51.4"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T00:00:00Z","timestamp":1354147200000},"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.1002777","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T22:30:16Z","timestamp":1354228216000},"page":"e1002777","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["Molecular Basis of Calcium-Sensitizing and Desensitizing Mutations of the Human Cardiac Troponin C Regulatory Domain: A Multi-Scale Simulation Study"],"prefix":"10.1371","volume":"8","author":[{"given":"Peter Michael","family":"Kekenes-Huskey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Lindert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James Andrew","family":"McCammon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2012,11,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1152\/physrev.2000.80.2.853","article-title":"Regulation of contraction in striated muscle","volume":"80","author":"AMA Gordon","year":"2000","journal-title":"Physiol Rev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s10741-005-5253-5","article-title":"Sarcomeric proteins and familial hypertrophic cardiomyopathy: linking mutations in structural proteins to complex cardiovascular phenotypes","volume":"10","author":"JCJ Tardiff","year":"2005","journal-title":"Heart Failure Rev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"30909","DOI":"10.1074\/jbc.M500287200","article-title":"Mutations in human cardiac Troponin I that are associated with restrictive cardiomyopathy affect basal ATPase activity and the calcium sensitivity of force development","volume":"280","author":"A Gomes","year":"2005","journal-title":"J Biol Chem"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s12265-011-9266-2","article-title":"How Do Mutations in Contractile Proteins Cause the Primary Familial Cardiomyopathies?","volume":"4","author":"SB Marston","year":"2011","journal-title":"J Cardio Trans Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/jhg.2009.138","article-title":"Molecular basis of hereditary cardiomyopathy: abnormalities in calcium sensitivity, stretch response, stress response and beyond","volume":"55","author":"A Kimura","year":"2010","journal-title":"J Hum Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1529\/biophysj.107.112896","article-title":"A novel mutant cardiac troponin C disrupts molecular motions critical for calcium binding affinity and cardiomyocyte contractility","volume":"94","author":"CC Lim","year":"2008","journal-title":"Biophys J"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"5140","DOI":"10.1073\/pnas.090098997","article-title":"Bepridil opens the regulatory N-terminal lobe of cardiac troponin C","volume":"97","author":"Y Li","year":"2000","journal-title":"Proc Natl Acad Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"27785","DOI":"10.1074\/jbc.M110.112326","article-title":"Predicting cardiomyopathic phenotypes by altering the Ca2+ affinity of cardiac troponin C","volume":"285","author":"MS Parvatiyar","year":"2010","journal-title":"The J Biol Chem"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"19090","DOI":"10.1074\/jbc.M109.007021","article-title":"A functional and structural study of troponin C mutations related to hypertrophic cardiomyopathy","volume":"284","author":"J Pinto","year":"2009","journal-title":"The J Biol Chem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"35341","DOI":"10.1074\/jbc.M405413200","article-title":"Designing Calcium-sensitizing Mutations in the Regulatory Domain of Cardiac Troponin C","volume":"279","author":"SB Tikunova","year":"2004","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10858-011-9546-9","article-title":"Visualizing the principal component of 1 H, 15 N-HSQC NMR spectral changes that reflect protein structural or functional properties: application to troponin C","volume":"51","author":"I Robertson","year":"2011","journal-title":"J Biomol NMR"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nature01780","article-title":"Structure of the core domain of human cardiac troponin in the Ca2+-saturated form","volume":"424","author":"S Takeda","year":"2003","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"12541","DOI":"10.1021\/bi010903k","article-title":"Temperature Dependence of Dynamics and Thermodynamics of the Regulatory Domain of Human Cardiac Troponin C","volume":"40","author":"L Spyracopoulos","year":"2001","journal-title":"Biochemistry"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"18032","DOI":"10.1021\/bi9816960","article-title":"Dynamics and Thermodynamics of the Regulatory Domain of Human Cardiac Troponin C in the Apo- and Calcium-Saturated States","volume":"37","author":"L Spyracopoulos","year":"1998","journal-title":"Biochemistry"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"12138","DOI":"10.1021\/bi971223d","article-title":"Calcium-Induced Structural Transition in the Regulatory Domain of Human Cardiac Troponin C,","volume":"36","author":"L Spyracopoulos","year":"1997","journal-title":"Biochemistry"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"8449","DOI":"10.1021\/jp212173f","article-title":"Dynamics and Calcium Association to the N-Terminal Regulatory Domain of Human Cardiac Troponin C: A Multiscale Computational Study","volume":"116","author":"S Lindert","year":"2012","journal-title":"J Phys Chem B"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/07391102.2011.10507378","article-title":"Molecular Dynamics and Docking Studies on Cardiac Troponin C","volume":"29","author":"JF Varughese","year":"2011","journal-title":"J Biomol Struct Dyn"},{"key":"ref18","article-title":"Millisecond-timescale simulations of Troponin C","author":"S Lindert","year":"2012","journal-title":"Biophys J"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1021\/bi3003007","article-title":"Structural and functional consequences of the cardiac troponin C L48Q Ca2+-sensitizing mutation","volume":"51","author":"D Wang","year":"2012","journal-title":"Biochemistry"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"9169","DOI":"10.1063\/1.1410978","article-title":"Calculating free energies using average force","volume":"115","author":"E Darve","year":"2001","journal-title":"J Chem Phys"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.yjmcc.2010.01.016","article-title":"Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: The basis of W7 as an inhibitor of cardiac muscle contraction","volume":"48","author":"M Oleszczuk","year":"2010","journal-title":"J Mol Cell Cardiol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1139\/o98-055","article-title":"The NMR angle on troponin C","volume":"76","author":"SMS Gagn'e","year":"1998","journal-title":"Biochem Cell Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/nsb1101-926","article-title":"Dynamic activation of protein function: a view emerging from NMR spectroscopy","volume":"8","author":"A Wand","year":"2001","journal-title":"Nat Struct Mol Biol"},{"key":"ref24","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"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"16036","DOI":"10.1021\/jp109908u","article-title":"Entropy Localization in Proteins","volume":"114","author":"DW Li","year":"2010","journal-title":"J Phys Chem B"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/prot.21679","article-title":"Electrostatic rate enhancement and transient complex of proteinprotein association","volume":"71","author":"R Alsallaq","year":"2008","journal-title":"Prot Func Bioinformatics"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1093\/oxfordjournals.jbchem.a135143","article-title":"Calcium binding to troponin C and troponin: effects of Mg2+, ionic strength and pH","volume":"97","author":"Y Ogawa","year":"1985","journal-title":"J Biochem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1002\/pro.5560071123","article-title":"The kinetic cycle of cardiac troponin C: Calcium binding and dissociation at site II trigger slow conformational rearrangements","volume":"7","author":"AL Hazard","year":"1998","journal-title":"Prot Sci"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1161\/hh0102.102269","article-title":"Myofilament Calcium Sensitivity in Skinned Rat Cardiac Trabeculae: Role of Interfilament Spacing","volume":"90","author":"JP Konhilas","year":"2001","journal-title":"Circ Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"6697","DOI":"10.1021\/bi011763h","article-title":"Effect of hydrophobic residue substitutions with glutamine on Ca2+ binding and exchange with the N-domain of troponin C","volume":"41","author":"S Tikunova","year":"2002","journal-title":"Biochemistry"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1432-1033.1977.tb11885.x","article-title":"The Protein Data Bank. A Computer-Based Archival File for Macromolecular Structures","volume":"80","author":"FC BERNSTEIN","year":"1977","journal-title":"Eur J Biochem"},{"key":"ref32","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":"ref33","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 Comp Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD","volume":"26","author":"J Phillips","year":"2005","journal-title":"J Comp Chem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"5823","DOI":"10.1021\/jp100926h","article-title":"Free energy calculations: An efficient adaptive biasing potential method","volume":"114","author":"B Dickson","year":"2010","journal-title":"J Phys Chem B"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1093\/bioinformatics\/btl461","article-title":"Bio3d: an R package for the comparative analysis of protein structures","volume":"22","author":"BJ Grant","year":"2006","journal-title":"Bioinformatics"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1002\/jcc.20303","article-title":"The GROMOS software for biomolecular simulation: GROMOS05","volume":"26","author":"MM Christen","year":"2005","journal-title":"J Comp Chem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/bip.360221211","article-title":"Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features","volume":"22","author":"WW Kabsch","year":"1983","journal-title":"Biopolymers"},{"key":"ref39","first-page":"317","article-title":"Vector geometry mapping. A method to characterize the conformation of helix-loop-helix calcium-binding proteins","volume":"173","author":"KLK Yap","year":"2002","journal-title":"Methods Mol Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1073\/pnas.181342398","article-title":"Electrostatics of nanosystems: Application to microtubules and the ribosome","volume":"98","author":"NA Baker","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"4522","DOI":"10.1021\/ja012750u","article-title":"General framework for studying the dynamics of folded and nonfolded proteins by NMR relaxation spectroscopy and MD simulation","volume":"124","author":"JJ Prompers","year":"2002","journal-title":"J Am Chem Soc"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/j.cpc.2010.07.022","article-title":"Browndye: A Software Package for Brownian Dynamics","volume":"181","author":"GA Huber","year":"2010","journal-title":"Comput Phys Commun"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"W522","DOI":"10.1093\/nar\/gkm276","article-title":"PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations","volume":"35","author":"TJ Dolinsky","year":"2007","journal-title":"Nucleic Acids Res"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,6]],"date-time":"2019-07-06T07:40:23Z","timestamp":1562398823000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002777"}},"subtitle":[],"editor":[{"given":"Roland L.","family":"Dunbrack","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2012,11,29]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,11,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002777","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,29]]}}}