{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:58:39Z","timestamp":1786121919381,"version":"build-2736575974"},"reference-count":79,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["757111"],"award-info":[{"award-number":["757111"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.bpj.2026.07.011","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:34:52Z","timestamp":1784129692000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping active-site conformational ensembles along competing catalytic pathways of the hairpin ribozyme"],"prefix":"10.1016","author":[{"given":"S\u00e9l\u00e8ne","family":"Forget","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-5699","authenticated-orcid":false,"given":"Guillaume","family":"Stirnemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bpj.2026.07.011_bib1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0092-8674(81)90390-1","article-title":"In vitro splicing of the ribosomal RNA precursor of tetrahymena: Involvement of a guanosine nucleotide in the excision of the intervening sequence","volume":"27","author":"Cech","year":"1981","journal-title":"Cell"},{"key":"10.1016\/j.bpj.2026.07.011_bib2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0092-8674(82)90414-7","article-title":"Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena","volume":"31","author":"Kruger","year":"1982","journal-title":"Cell"},{"key":"10.1016\/j.bpj.2026.07.011_bib3","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/0092-8674(83)90117-4","article-title":"The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme","volume":"35","author":"Guerrier-Takada","year":"1983","journal-title":"Cell"},{"key":"10.1016\/j.bpj.2026.07.011_bib4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrg3841","article-title":"The RNA World: molecular cooperation at the origins of life","volume":"16","author":"Higgs","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.bpj.2026.07.011_bib5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/418222a","article-title":"The chemical repertoire of natural ribozymes","volume":"418","author":"Doudna","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2026.07.011_bib6","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1126\/science.1178084","article-title":"Widespread Occurrence of Self-Cleaving Ribozymes","volume":"326","author":"Webb","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.bpj.2026.07.011_bib7","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0968-0004(03)00191-9","article-title":"The origins of RNA catalysis in ribozymes","volume":"28","author":"Lilley","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.bpj.2026.07.011_bib8","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrm1647","article-title":"The catalytic diversity of RNAs","volume":"6","author":"Fedor","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib9","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.tibs.2015.09.001","article-title":"Chemistry and Biology of Self-Cleaving Ribozymes","volume":"40","author":"Jimenez","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.bpj.2026.07.011_bib10","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1006\/jmbi.2000.3560","article-title":"Structure and function of the hairpin ribozyme","volume":"297","author":"Fedor","year":"2000","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib11","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/iub.575","article-title":"The many faces of the hairpin ribozyme: Structural and functional variants of a small catalytic rna","volume":"64","author":"M\u00fcller","year":"2012","journal-title":"IUBMB Life"},{"key":"10.1016\/j.bpj.2026.07.011_bib12","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1093\/nar\/20.11.2835","article-title":"Extensive phosphorothioate substitution yields highly active and nuclease-resistant hairpin ribozymes","volume":"20","author":"Chowrira","year":"1992","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.07.011_bib13","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S1074-5521(97)90323-9","article-title":"A unique mechanism for RNA catalysis: the role of metal cofactors in hairpin ribozyme cleavage","volume":"4","author":"Hampel","year":"1997","journal-title":"Chem. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib14","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S1074-5521(97)90247-7","article-title":"An unusual pH-independent and metal-ion-independent mechanism for hairpin ribozyme catalysis","volume":"4","author":"Nesbitt","year":"1997","journal-title":"Chem. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib15","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1093\/nar\/25.19.3760","article-title":"Metal Ions Play a Passive Role in the Hairpin Ribozyme Catalysed Reaction","volume":"25","author":"Young","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.07.011_bib16","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1006\/jmbi.1999.2543","article-title":"The internal equilibrium of the hairpin ribozyme: temperature, ion and pH effects","volume":"286","author":"Nesbitt","year":"1999","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jmb.2004.04.067","article-title":"Role of an Active Site Guanine in Hairpin Ribozyme Catalysis Probed by Exogenous Nucleobase Rescue","volume":"340","author":"Kuzmin","year":"2004","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib18","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jmb.2005.04.005","article-title":"Role of an Active Site Adenine in Hairpin Ribozyme Catalysis","volume":"349","author":"Kuzmin","year":"2005","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib19","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/35071009","article-title":"Crystal structure of a hairpin ribozyme\u2013inhibitor complex with implications for catalysis","volume":"410","author":"Rupert","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2026.07.011_bib20","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1021\/bi051887k","article-title":"Water in the Active Site of an All-RNA Hairpin Ribozyme and Effects of Gua8 Base Variants on the Geometry of Phosphoryl Transfer","volume":"45","author":"Salter","year":"2006","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2026.07.011_bib21","doi-asserted-by":"crossref","first-page":"6093","DOI":"10.1021\/ja900450h","article-title":"Identification of an Imino Group Indispensable for Cleavage by a Small Ribozyme","volume":"131","author":"Spitale","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bpj.2026.07.011_bib22","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1261\/rna.1055308","article-title":"Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozyme","volume":"14","author":"MacElrevey","year":"2008","journal-title":"RNA"},{"key":"10.1016\/j.bpj.2026.07.011_bib23","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1021\/bi027273m","article-title":"Mechanistic Considerations for General Acid-Base Catalysis by RNA: Revisiting the Mechanism of the Hairpin Ribozyme","volume":"42","author":"Bevilacqua","year":"2003","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2026.07.011_bib24","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1261\/rna.11706","article-title":"Nucleobase catalysis in the hairpin ribozyme","volume":"12","author":"Wilson","year":"2006","journal-title":"RNA"},{"key":"10.1016\/j.bpj.2026.07.011_bib25","doi-asserted-by":"crossref","first-page":"16717","DOI":"10.1021\/ja3067429","article-title":"General Acid\u2013Base Catalysis Mediated by Nucleobases in the Hairpin Ribozyme","volume":"134","author":"Kath-Schorr","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bpj.2026.07.011_bib26","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1126\/science.1076093","article-title":"Transition State Stabilization by a Catalytic RNA","volume":"298","author":"Rupert","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.bpj.2026.07.011_bib27","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nchembio.156","article-title":"Direct measurement of the ionization state of an essential guanine in the hairpin ribozyme","volume":"5","author":"Liu","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/bip.10519","article-title":"Catalytic roles for proton transfer and protonation in ribozymes","volume":"73","author":"Bevilacqua","year":"2004","journal-title":"Biopolymers"},{"key":"10.1016\/j.bpj.2026.07.011_bib29","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkag046","article-title":"Critical structural perturbations of ribozyme active sites induced by 2\u2019-O-methylation commonly used in structural studies","volume":"54","author":"Forget","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.07.011_bib30","doi-asserted-by":"crossref","first-page":"6642","DOI":"10.1021\/jp1001258","article-title":"Extensive Molecular Dynamics Simulations Showing That Canonical G8 and Protonated A38H + Forms Are Most Consistent with Crystal Structures of Hairpin Ribozyme","volume":"114","author":"Ml\u00fdnsk\u00fd","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib31","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.1021\/jp512069n","article-title":"Reactive Conformation of the Active Site in the Hairpin Ribozyme Achieved by Molecular Dynamics Simulations with \u03f5\/\u03b6 Force Field Reparametrizations","volume":"119","author":"Ml\u00fdnsk\u00fd","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib32","doi-asserted-by":"crossref","first-page":"20886","DOI":"10.1039\/C8CP03142H","article-title":"Mechanistic role of nucleobases in self-cleavage catalysis of hairpin ribozyme at ambient versus high-pressure conditions","volume":"20","author":"Kumar","year":"2018","journal-title":"Phys. Chem. Chem. Phys."},{"key":"10.1016\/j.bpj.2026.07.011_bib33","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1021\/ct401015e","article-title":"Comparison of ab Initio, DFT, and Semiempirical QM\/MM Approaches for Description of Catalytic Mechanism of Hairpin Ribozyme","volume":"10","author":"Ml\u00fdnsk\u00fd","year":"2014","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2026.07.011_bib34","doi-asserted-by":"crossref","first-page":"13911","DOI":"10.1021\/jp206963g","article-title":"QM\/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms","volume":"115","author":"Ml\u00fdnsk\u00fd","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib35","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1261\/rna.863108","article-title":"Electrostatic interactions in the hairpin ribozyme account for the majority of the rate acceleration without chemical participation by nucleobases","volume":"14","author":"Nam","year":"2008","journal-title":"RNA"},{"key":"10.1016\/j.bpj.2026.07.011_bib36","doi-asserted-by":"crossref","first-page":"4906","DOI":"10.1021\/acs.jpcb.0c03768","article-title":"Deciphering the Self-Cleavage Reaction Mechanism of Hairpin Ribozyme","volume":"124","author":"Kumar","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib37","doi-asserted-by":"crossref","first-page":"11869","DOI":"10.1021\/acs.jpcb.1c06546","article-title":"Investigation of the pKa of the Nucleophilic O2\u2019 of the Hairpin Ribozyme","volume":"125","author":"Veenis","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib38","doi-asserted-by":"crossref","first-page":"6263","DOI":"10.1021\/acs.jctc.4c00294","article-title":"Simulation-Guided Conformational Space Exploration to Assess Reactive Conformations of a Ribozyme","volume":"20","author":"Forget","year":"2024","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2026.07.011_bib39","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1021\/ja0759141","article-title":"Quantum Mechanical\/Molecular Mechanical Simulation Study of the Mechanism of Hairpin Ribozyme Catalysis","volume":"130","author":"Nam","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bpj.2026.07.011_bib40","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"10.1016\/j.bpj.2026.07.011_bib41","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.cpc.2013.09.018","article-title":"PLUMED 2: New feathers for an old bird","volume":"185","author":"Tribello","year":"2014","journal-title":"Comput. Phys. Commun."},{"key":"10.1016\/j.bpj.2026.07.011_bib42","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41592-019-0506-8","article-title":"Promoting transparency and reproducibility in enhanced molecular simulations","volume":"16","year":"2019","journal-title":"Nat. Methods"},{"key":"10.1016\/j.bpj.2026.07.011_bib43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD \u2013 Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"10.1016\/j.bpj.2026.07.011_bib44","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1021\/acs.jctc.1c01081","article-title":"Human Learning for Molecular Simulations: The Collective Variables Dashboard in VMD","volume":"18","author":"H\u00e9nin","year":"2022","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2026.07.011_bib45","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/jcc.21787","article-title":"MDAnalysis: A toolkit for the analysis of molecular dynamics simulations","volume":"32","author":"Michaud-Agrawal","year":"2011","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bpj.2026.07.011_bib46","series-title":"Python in Science Conference","doi-asserted-by":"crossref","first-page":"98","DOI":"10.25080\/Majora-629e541a-00e","article-title":"MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations","author":"Gowers","year":"2016"},{"key":"10.1016\/j.bpj.2026.07.011_bib47","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1261\/rna.067678.118","article-title":"Barnaba: software for analysis of nucleic acid structures and trajectories","volume":"25","author":"Bottaro","year":"2019","journal-title":"RNA"},{"key":"10.1016\/j.bpj.2026.07.011_bib48","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1021\/ct400154j","article-title":"Toward Improved Description of DNA Backbone: Revisiting Epsilon and Zeta Torsion Force Field Parameters","volume":"9","author":"Zgarbov\u00e1","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2026.07.011_bib49","doi-asserted-by":"crossref","first-page":"9020","DOI":"10.1021\/jp8001614","article-title":"Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations","volume":"112","author":"Joung","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib50","series-title":"Gaussian\u02dc16 Revision C.01","author":"Frisch","year":"2016"},{"key":"10.1016\/j.bpj.2026.07.011_bib51","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1021\/acs.jcim.3c01153","article-title":"AmberTools","volume":"63","author":"Case","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bpj.2026.07.011_bib52","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N.log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.bpj.2026.07.011_bib53","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: A linear constraint solver for molecular simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bpj.2026.07.011_bib54","doi-asserted-by":"crossref","first-page":"13749","DOI":"10.1073\/pnas.0506346102","article-title":"Replica exchange with solute tempering: A method for sampling biological systems in explicit water","volume":"102","author":"Liu","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2026.07.011_bib55","doi-asserted-by":"crossref","first-page":"9431","DOI":"10.1021\/jp204407d","article-title":"Replica Exchange with Solute Scaling: A More Efficient Version of Replica Exchange with Solute Tempering (REST2)","volume":"115","author":"Wang","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib56","doi-asserted-by":"crossref","first-page":"13306","DOI":"10.1093\/nar\/gku972","article-title":"The role of nucleobase interactions in RNA structure and dynamics","volume":"42","author":"Bottaro","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.07.011_bib57","article-title":"Clustering data by reordering them","author":"Descamps","year":"2025","journal-title":"arXiv"},{"key":"10.1016\/j.bpj.2026.07.011_bib58","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1021\/acs.chemrev.7b00427","article-title":"RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview","volume":"118","author":"\u0160poner","year":"2018","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bpj.2026.07.011_bib59","author":"Roeder"},{"key":"10.1016\/j.bpj.2026.07.011_bib60","doi-asserted-by":"crossref","first-page":"13498","DOI":"10.1074\/jbc.M700451200","article-title":"Functional Analysis of Hairpin Ribozyme Active Site Architecture","volume":"282","author":"Cottrell","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bpj.2026.07.011_bib61","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1261\/rna.2473711","article-title":"Do the hairpin and VS ribozymes share a common catalytic mechanism based on general acid\u2013base catalysis? A critical assessment of available experimental data","volume":"17","author":"Wilson","year":"2011","journal-title":"RNA"},{"key":"10.1016\/j.bpj.2026.07.011_bib62","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1074-5521(02)00130-8","article-title":"Rescue of an Abasic Hairpin Ribozyme by Cationic Nucleobases","volume":"9","author":"Lebruska","year":"2002","journal-title":"Chem. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib63","doi-asserted-by":"crossref","first-page":"17658","DOI":"10.1074\/jbc.M111.234906","article-title":"The pH Dependence of Hairpin Ribozyme Catalysis Reflects Ionization of an Active Site Adenine","volume":"286","author":"Cottrell","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bpj.2026.07.011_bib64","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1021\/ar900093g","article-title":"Molecular Dynamics and Quantum Mechanics of RNA: Conformational and Chemical Change We Can Believe","volume":"43","author":"Ditzler","year":"2010","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.bpj.2026.07.011_bib65","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1021\/acscatal.7b02976","article-title":"Elucidation of Catalytic Strategies of Small Nucleolytic Ribozymes from Comparative Analysis of Active Sites","volume":"8","author":"Seith","year":"2018","journal-title":"ACS Catal."},{"key":"10.1016\/j.bpj.2026.07.011_bib66","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1261\/rna.510807","article-title":"A comparison of vanadate to a 2\u2019\u20135\u2019 linkage at the active site of a small ribozyme suggests a role for water in transition-state stabilization","volume":"13","author":"Torelli","year":"2007","journal-title":"RNA"},{"key":"10.1016\/j.bpj.2026.07.011_bib67","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/nsmb842","article-title":"Observation of internal cleavage and ligation reactions of a ribozyme","volume":"11","author":"Nahas","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.bpj.2026.07.011_bib68","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaf1366","article-title":"Revealing hidden protonated conformational states in RNA dynamic ensembles","volume":"53","author":"Geng","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bpj.2026.07.011_bib69","doi-asserted-by":"crossref","first-page":"12261","DOI":"10.1002\/ange.201206000","article-title":"Ligand- and pH-Induced Conformational Changes of RNA Domain Helix 69 Revealed by 2-Aminopurine Fluorescence","volume":"124","author":"Sakakibara","year":"2012","journal-title":"Angew. Chem., Int. Ed."},{"key":"10.1016\/j.bpj.2026.07.011_bib70","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2322040121","article-title":"Prebiotic Chemical Reactivity in Solution with Quantum Accuracy and Microsecond Sampling Using Neural Network Potentials","volume":"121","author":"Benayad","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2026.07.011_bib71","doi-asserted-by":"crossref","DOI":"10.1002\/chem.202502428","article-title":"Deciphering the Molecular Mechanisms of Phosphoester Bond Formation in Abiotic Conditions With Reactive Neural Network Potentials","volume":"32","author":"Benayad","year":"2026","journal-title":"Chem. Eur J."},{"key":"10.1016\/j.bpj.2026.07.011_bib72","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1021\/jp972182y","article-title":"Phosphate Ester Hydrolysis in Aqueous Solution: Associative versus Dissociative Mechanisms","volume":"102","author":"Flori\u00e1n","year":"1998","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bpj.2026.07.011_bib73","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1021\/ja5082712","article-title":"Resolving Apparent Conflicts between Theoretical and Experimental Models of Phosphate Monoester Hydrolysis","volume":"137","author":"Duarte","year":"2015","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bpj.2026.07.011_bib74","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1021\/cr0503106","article-title":"Electrostatic Basis for Enzyme Catalysis","volume":"106","author":"Warshel","year":"2006","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bpj.2026.07.011_bib75","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1146\/annurev-physchem-083122-125941","article-title":"Enhanced Sampling with Machine Learning","volume":"75","author":"Mehdi","year":"2024","journal-title":"Annu. Rev. Phys. Chem."},{"key":"10.1016\/j.bpj.2026.07.011_bib76","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1039\/D5SC06402C","article-title":"Latent thermodynamic flows: unified representation learning and generative modeling of temperature-dependent behaviors from limited data","volume":"17","author":"Qiu","year":"2026","journal-title":"Chem. Sci."},{"key":"10.1016\/j.bpj.2026.07.011_bib77","doi-asserted-by":"crossref","first-page":"10692","DOI":"10.1021\/acs.jctc.5c00738","article-title":"Hamiltonian Replica Exchange Augmented with Diffusion-Based Generative Models and Importance Sampling to Assess Biomolecular Conformational Basins and Barriers","volume":"21","author":"Benayad","year":"2025","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bpj.2026.07.011_bib78","doi-asserted-by":"crossref","DOI":"10.1063\/5.0260078","article-title":"From QM\/MM to ML\/MM: A new era in multiscale modeling","volume":"6","author":"Grassano","year":"2025","journal-title":"Chem. Phys. Rev."},{"key":"10.1016\/j.bpj.2026.07.011_bib79","doi-asserted-by":"crossref","DOI":"10.1063\/5.0251501","article-title":"PLUMED Tutorials: A collaborative, community-driven learning ecosystem","volume":"162","author":"Tribello","year":"2025","journal-title":"J. Chem. Phys."}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349526004923?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349526004923?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T07:12:01Z","timestamp":1786086721000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006349526004923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":79,"alternative-id":["S0006349526004923"],"URL":"https:\/\/doi.org\/10.1016\/j.bpj.2026.07.011","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mapping active-site conformational ensembles along competing catalytic pathways of the hairpin ribozyme","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bpj.2026.07.011","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"}]}}