{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:39:38Z","timestamp":1793281178025,"version":"4.5.0"},"reference-count":68,"publisher":"Elsevier BV","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.bpj.2026.09.002","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:52:47Z","timestamp":1788533567000},"page":"5739-5751","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low-dimensional energetic landscape governing Ca2+ binding in troponin C"],"prefix":"10.1016","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7473-8401","authenticated-orcid":false,"given":"Abdul","family":"Basit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bpj.2026.09.002_bib1","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":"Gordon","year":"2000","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.bpj.2026.09.002_bib2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.yjmcc.2010.10.025","article-title":"Calcium binding kinetics of troponin C strongly modulate cooperative activation and tension kinetics in cardiac muscle","volume":"50","author":"Kreutziger","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.bpj.2026.09.002_bib3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.gene.2015.07.074","article-title":"Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs","volume":"571","author":"Li","year":"2015","journal-title":"Gene"},{"key":"10.1016\/j.bpj.2026.09.002_bib4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10974-019-09513-1","article-title":"Troponin structure and function: a view of recent progress","volume":"41","author":"Marston","year":"2020","journal-title":"J. Muscle Res. Cell Motil."},{"key":"10.1016\/j.bpj.2026.09.002_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.100350","article-title":"Binding of calcium and magnesium to human cardiac troponin C","volume":"296","author":"Rayani","year":"2021","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bpj.2026.09.002_bib6","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1021\/cr00023a004","article-title":"Free energy calculations: applications to chemical and biochemical phenomena","volume":"93","author":"Kollman","year":"1993","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bpj.2026.09.002_bib7","doi-asserted-by":"crossref","DOI":"10.1063\/1.2978177","article-title":"Statistically optimal analysis of samples from multiple equilibrium states","volume":"129","author":"Shirts","year":"2008","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.bpj.2026.09.002_bib8","doi-asserted-by":"crossref","DOI":"10.33011\/livecoms.2.1.18378","article-title":"Best practices for alchemical free energy calculations","volume":"2","author":"Mey","year":"2020","journal-title":"Living J. Comput. Mol. Sci."},{"key":"10.1016\/j.bpj.2026.09.002_bib9","doi-asserted-by":"crossref","first-page":"11915","DOI":"10.1074\/jbc.M116.770776","article-title":"Changes in the dynamics of the cardiac troponin C molecule explain the effects of Ca2+-sensitizing mutations","volume":"292","author":"Stevens","year":"2017","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bpj.2026.09.002_bib10","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fmolb.2019.00068","article-title":"Computational studies of cardiac and skeletal troponin","volume":"6","author":"Bowman","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.bpj.2026.09.002_bib11","doi-asserted-by":"crossref","first-page":"7213","DOI":"10.1080\/07391102.2020.1810125","article-title":"Calcium ion binding to calmodulin: binding free energy calculation using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method by incorporating implicit polarization","volume":"39","author":"Basit","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.bpj.2026.09.002_bib12","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1021\/acs.jcim.2c00428","article-title":"Calcium ion binding to the mutants of calmodulin: a structure-based computational predictive model of binding affinity using a charge scaling approach in molecular dynamics simulation","volume":"62","author":"Basit","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.09.002_bib13","doi-asserted-by":"crossref","first-page":"8736","DOI":"10.1021\/acs.jpcb.3c02337","article-title":"Modulation of structure and dynamics of cardiac troponin by phosphorylation and mutations revealed by molecular dynamics simulations","volume":"127","author":"Yang","year":"2023","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.09.002_bib14","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1002\/prot.26743","article-title":"Prediction of Ca2+ binding site in proteins with a fast and accurate method based on statistical mechanics and analysis of crystal structures","volume":"93","author":"Basit","year":"2025","journal-title":"Proteins"},{"key":"10.1016\/j.bpj.2026.09.002_bib15","doi-asserted-by":"crossref","DOI":"10.1007\/s00894-026-06846-w","article-title":"Evolutionary and physics-guided modulation of Ca2+ sensitivity in cardiac troponin C","volume":"32","author":"Basit","year":"2026","journal-title":"J. Mol. Model."},{"key":"10.1016\/j.bpj.2026.09.002_bib16","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1021\/jacs.0c01329","article-title":"Thermodynamics of transition metal ion binding to proteins","volume":"142","author":"Song","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bpj.2026.09.002_bib17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1021\/acsphyschemau.1c00039","article-title":"Binding energy and free energy of calcium ion to calmodulin EF-hands with the drude polarizable force field","volume":"2","author":"Tan","year":"2022","journal-title":"ACS Phys. Chem. Au"},{"key":"10.1016\/j.bpj.2026.09.002_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0096202","article-title":"Prediction and analysis of canonical EF hand loop and qualitative estimation of Ca2+ binding affinity","volume":"9","author":"Mazumder","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.bpj.2026.09.002_bib19","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1021\/acs.jcim.2c01411","article-title":"Molecular Insights into the Calcium Binding in Troponin C through a Molecular Dynamics Study","volume":"63","author":"Smith","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.09.002_bib20","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1021\/acs.chemrev.6b00440","article-title":"Metal ion modeling using classical mechanics","volume":"117","author":"Li","year":"2017","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bpj.2026.09.002_bib21","doi-asserted-by":"crossref","first-page":"6966","DOI":"10.1021\/jp3007365","article-title":"Ion binding sites and their representations by reduced models","volume":"116","author":"Roux","year":"2012","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.09.002_bib22","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1021\/jz201501a","article-title":"Aksimentiev A. Improved parametrization of Li+, Na+, K+, and Mg2+ ions for all-atom molecular dynamics simulations of nucleic acid systems","volume":"3","author":"Yoo","year":"2012","journal-title":"J. Phys. Chem. Lett."},{"key":"10.1016\/j.bpj.2026.09.002_bib23","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1021\/acs.jcim.1c00419","article-title":"Adaptative steered molecular dynamics study of mutagenesis effects on calcium affinity in the regulatory domain of cardiac troponin C","volume":"61","author":"Hantz","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.09.002_bib24","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.1021\/acs.jcim.2c01132","article-title":"Computational exploration and characterization of potential calcium sensitizing mutations in cardiac troponin C","volume":"62","author":"Hantz","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.09.002_bib25","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0022-2836(02)00442-4","article-title":"Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations","volume":"320","author":"Guerois","year":"2002","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.09.002_bib26","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/prot.22921","article-title":"Role of conformational sampling in computing mutation-induced changes in protein structure and stability","volume":"79","author":"Kellogg","year":"2011","journal-title":"Proteins"},{"key":"10.1016\/j.bpj.2026.09.002_bib27","doi-asserted-by":"crossref","first-page":"290a","DOI":"10.1016\/j.bpj.2020.11.1863","article-title":"Geometric deep learning on biomolecular structure","volume":"120","author":"Townshend","year":"2021","journal-title":"Biophys. J."},{"key":"10.1016\/j.bpj.2026.09.002_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2023.125866","article-title":"Machine learning-based modulation of Ca2+-binding affinity in EF-hand proteins and comparative structural insights into site-specific cooperative binding","volume":"248","author":"Mazumder","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.bpj.2026.09.002_bib29","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.cell.2013.03.034","article-title":"Allostery in disease and in drug discovery","volume":"153","author":"Nussinov","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.bpj.2026.09.002_bib30","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-biophys-050511-102222","article-title":"Allostery and the Monod-Wyman-Changeux model after 50 years","volume":"41","author":"Changeux","year":"2012","journal-title":"Annu. Rev. Biophys."},{"key":"10.1016\/j.bpj.2026.09.002_bib31","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s42254-021-00314-5","article-title":"Physics-informed machine learning","volume":"3","author":"Karniadakis","year":"2021","journal-title":"Nat. Rev. Phys."},{"key":"10.1016\/j.bpj.2026.09.002_bib32","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.1021\/acs.jcim.5c00341","article-title":"Including physics-informed atomization constraints in neural networks for reactive chemistry","volume":"65","author":"Zhang","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.09.002_bib33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/BJ20070255","article-title":"Structures and metal-ion-binding properties of the Ca2+-binding helix\u2013loop\u2013helix EF-hand motifs","volume":"405","author":"Gifford","year":"2007","journal-title":"Biochem. J."},{"key":"10.1016\/j.bpj.2026.09.002_bib34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1021\/ar100110d","article-title":"Relating form and function of EF-hand calcium binding proteins","volume":"44","author":"Chazin","year":"2011","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.bpj.2026.09.002_bib35","doi-asserted-by":"crossref","first-page":"6390","DOI":"10.1021\/acs.jpcb.1c01269","article-title":"Structural changes beyond the EF-hand contribute to apparent calcium binding affinities: insights from parvalbumins","volume":"125","author":"Immadisetty","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.09.002_bib36","doi-asserted-by":"crossref","first-page":"18149","DOI":"10.1039\/D3CP01978K","article-title":"Electrostatic interactions\u2013key determinants of the metal selectivity in La3+ and Ca2+ binding proteins","volume":"25","author":"Angelova","year":"2023","journal-title":"Phys. Chem. Chem. Phys."},{"key":"10.1016\/j.bpj.2026.09.002_bib37","doi-asserted-by":"crossref","first-page":"7628","DOI":"10.1021\/jacs.3c13981","article-title":"Flexibility of binding site is essential to the Ca2+ selectivity in EF-hand calcium-binding proteins","volume":"146","author":"Lai","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bpj.2026.09.002_bib38","doi-asserted-by":"crossref","first-page":"6620","DOI":"10.1073\/pnas.0810961106","article-title":"Dynamical networks in tRNA: protein complexes","volume":"106","author":"Sethi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2026.09.002_bib39","doi-asserted-by":"crossref","first-page":"27035","DOI":"10.1074\/jbc.273.42.27035","article-title":"Electrostatic origin of the catalytic power of enzymes and the role of preorganized active sites","volume":"273","author":"Warshel","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bpj.2026.09.002_bib40","doi-asserted-by":"crossref","first-page":"21441","DOI":"10.1073\/pnas.1015661107","article-title":"Free energy profiles from single-molecule pulling experiments","volume":"107","author":"Hummer","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2026.09.002_bib41","doi-asserted-by":"crossref","first-page":"6871","DOI":"10.1021\/acs.chemrev.5c00507","article-title":"Introduction: electric fields in chemistry and biology","volume":"125","author":"Boxer","year":"2025","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bpj.2026.09.002_bib42","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1126\/science.1749933","article-title":"The energy landscapes and motions of proteins","volume":"254","author":"Frauenfelder","year":"1991","journal-title":"Science"},{"key":"10.1016\/j.bpj.2026.09.002_bib43","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1146\/annurev.physchem.48.1.545","article-title":"Theory of protein folding: the energy landscape perspective","volume":"48","author":"Onuchic","year":"1997","journal-title":"Annu. Rev. Phys. Chem."},{"key":"10.1016\/j.bpj.2026.09.002_bib44","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.1021\/jp037421y","article-title":"Describing protein folding kinetics by molecular dynamics simulations. 1. Theory","volume":"108","author":"Swope","year":"2004","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.09.002_bib45","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.sbi.2014.04.002","article-title":"Markov state models of biomolecular conformational dynamics","volume":"25","author":"Chodera","year":"2014","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.bpj.2026.09.002_bib46","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1146\/annurev-physchem-040215-112215","article-title":"Reaction coordinates and mechanistic hypothesis tests","volume":"67","author":"Peters","year":"2016","journal-title":"Annu. Rev. Phys. Chem."},{"key":"10.1016\/j.bpj.2026.09.002_bib47","doi-asserted-by":"crossref","first-page":"5649","DOI":"10.1021\/acs.jctc.3c00660","article-title":"Kinetics from metadynamics: Principles, applications, and outlook","volume":"19","author":"Ray","year":"2023","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.bpj.2026.09.002_bib48","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1021\/acs.jpcb.3c08304","article-title":"Thermodynamically optimized machine-learned reaction coordinates for hydrophobic ligand dissociation","volume":"128","author":"Beyerle","year":"2024","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.09.002_bib49","doi-asserted-by":"crossref","DOI":"10.1063\/5.0176078","article-title":"Reaction coordinate flows for model reduction of molecular kinetics","volume":"160","author":"Wu","year":"2024","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.bpj.2026.09.002_bib50","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1088\/1367-2630\/7\/1\/034","article-title":"Position-dependent diffusion coefficients and free energies from Bayesian analysis of equilibrium and replica molecular dynamics simulations","volume":"7","author":"Hummer","year":"2005","journal-title":"New J. Phys."},{"key":"10.1016\/j.bpj.2026.09.002_bib51","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1137\/110858616","article-title":"A variational approach to modeling slow processes in stochastic dynamical systems","volume":"11","author":"No\u00e9","year":"2013","journal-title":"Multiscale Model. Simul."},{"key":"10.1016\/j.bpj.2026.09.002_bib52","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":"Monod","year":"1965","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.09.002_bib53","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":"Tikunova","year":"2002","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2026.09.002_bib54","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":"Tikunova","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bpj.2026.09.002_bib55","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":"Lim","year":"2008","journal-title":"Biophys. J."},{"key":"10.1016\/j.bpj.2026.09.002_bib56","doi-asserted-by":"crossref","first-page":"27785","DOI":"10.1074\/jbc.M110.112326","article-title":"Predicting cardiomyopathic phenotypes by altering Ca2+ affinity of cardiac troponin C","volume":"285","author":"Parvatiyar","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bpj.2026.09.002_bib57","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.abb.2013.02.006","article-title":"Structural and functional consequences of cardiac troponin C L57Q and I61Q Ca2+-desensitizing variants","volume":"535","author":"Wang","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.bpj.2026.09.002_bib58","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.abb.2014.03.004","article-title":"Molecular and functional consequences of mutations in the central helix of cardiac troponin C","volume":"548","author":"Swindle","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.bpj.2026.09.002_bib59","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3389\/fphys.2015.00242","article-title":"Knock-in mice harboring a Ca2+ desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy","volume":"6","author":"McConnell","year":"2015","journal-title":"Front. Physiol."},{"key":"10.1016\/j.bpj.2026.09.002_bib60","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":"Spyracopoulos","year":"1997","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2026.09.002_bib61","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/256705a0","article-title":"Principles of protein\u2013protein recognition","volume":"256","author":"Chothia","year":"1975","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2026.09.002_bib62","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1359-0278(97)00024-2","article-title":"Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential","volume":"2","author":"Bahar","year":"1997","journal-title":"Fold Des."},{"key":"10.1016\/j.bpj.2026.09.002_bib63","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0006-3495(01)76033-X","article-title":"Anisotropy of fluctuation dynamics of proteins with an elastic network model","volume":"80","author":"Atilgan","year":"2001","journal-title":"Biophys. J."},{"key":"10.1016\/j.bpj.2026.09.002_bib64","doi-asserted-by":"crossref","first-page":"2006.0019","DOI":"10.1038\/msb4100063","article-title":"Residues crucial for maintaining short paths in network communication mediate signaling in proteins","volume":"2","author":"Del Sol","year":"2006","journal-title":"Mol. Syst. Biol."},{"key":"10.1016\/j.bpj.2026.09.002_bib65","series-title":"Networks","author":"Newman","year":"2018"},{"key":"10.1016\/j.bpj.2026.09.002_bib66","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1093\/bioinformatics\/btab187","article-title":"ProDy 2.0: increased scale and scope after 10 years of protein dynamics modelling with Python","volume":"37","author":"Zhang","year":"2021","journal-title":"Bioinformatics"},{"key":"10.1016\/j.bpj.2026.09.002_bib67","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0047-259X(03)00096-4","article-title":"A well-conditioned estimator for large-dimensional covariance matrices","volume":"88","author":"Ledoit","year":"2004","journal-title":"J. Multivar. Anal."},{"key":"10.1016\/j.bpj.2026.09.002_bib68","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1214\/09-SS054","article-title":"A survey of cross-validation procedures for model selection","volume":"4","author":"Arlot","year":"2010","journal-title":"Stat. Surv."}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349526006077?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349526006077?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:07:02Z","timestamp":1793279222000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006349526006077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":68,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["S0006349526006077"],"URL":"https:\/\/doi.org\/10.1016\/j.bpj.2026.09.002","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Low-dimensional energetic landscape governing Ca2+ binding in troponin C","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bpj.2026.09.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Biophysical Society. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}