{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T08:48:12Z","timestamp":1792399692904,"version":"4.4.0"},"reference-count":109,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["514664767"],"award-info":[{"award-number":["514664767"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["IM141\/1-3"],"award-info":[{"award-number":["IM141\/1-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["318763901"],"award-info":[{"award-number":["318763901"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Diabetes, Digestive, and Kidney Diseases","award":["R01DK115563"],"award-info":[{"award-number":["R01DK115563"]}]},{"name":"Martin-Luther-Universit\u00e4t Halle-Wittenberg Universit\u00e4ts- und Landesbibliothek Sachsen-Anhalt Zeitschriftenstelle"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Methyl-CpG binding domain 2 (MBD2) is a critical epigenetic regulator that selectively binds methylated CpG dinucleotides, key marks controlling gene regulation and chromatin organization. Understanding the interactions and conformational dynamics underlying this high selectivity is essential to elucidate MBD2\u2019s regulatory role. Here, using extensive classical MD simulations, we explored the formation of the MBD2\u2013mCpG recognition complex. By initially positioning MBD2 one base pair downstream of its target, we observed its transition to the target site within microseconds. Notably, upon binding, MBD2 adopts two distinct stable conformations: a primary state closely resembling the X-ray crystal structure, and a secondary state of reduced affinity that nevertheless retains comparable selectivity for mCpG. Our results establish S189 as a key macro-switch; loss of its interaction with the methylcytosine backbone shifts the equilibrium toward the secondary state. This is corroborated by MD simulations of the S189A mutant, which preferentially adopts the secondary state-like conformation. Complementary NMR experiments confirm that S189A mutation does not alter mCpG selectivity, while fluorescence polarization measurements reveal a reduced binding affinity, consistent with our MD simulations results. Together, these findings indicate that MBD2 binding to methylated CpG involves a bistable equilibrium, providing new insights into how high affinity and adaptability are balanced in epigenetic recognition. In a broader context, our findings suggest that such alternative bound-state equilibria may represent an inherent feature of specific protein\u2013DNA complexes.<\/jats:p>","DOI":"10.1093\/nar\/gkag952","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T08:33:17Z","timestamp":1792398797000},"source":"Crossref","is-referenced-by-count":0,"title":["Exploring the bistable equilibrium of methylated CpG DNA recognition by the MBD2 protein"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4694-320X","authenticated-orcid":false,"given":"Senta","family":"Volkenandt","sequence":"first","affiliation":[{"name":"Computer Chemistry Center, Friedrich-Alexander-Universit\u00e4t (FAU) Erlangen-N\u00fcrnberg , N\u00e4gelsbachstrasse 25, 91052 Erlangen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Belyaeva","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery and Institute for Medical Physics and Biophysics, Leipzig University Medical School , 04103 Leipzig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torry","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, NC 27599, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0550-4852","authenticated-orcid":false,"given":"Matthias","family":"Elgeti","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery and Institute for Medical Physics and Biophysics, Leipzig University Medical School , 04103 Leipzig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-7020","authenticated-orcid":false,"given":"Ralf","family":"Metzler","sequence":"additional","affiliation":[{"name":"Institute of Physics and Astronomy, University of Potsdam , Potsdam 14476 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9820-4578","authenticated-orcid":false,"given":"Petra","family":"Imhof","sequence":"additional","affiliation":[{"name":"Computer Chemistry Center, Friedrich-Alexander-Universit\u00e4t (FAU) Erlangen-N\u00fcrnberg , N\u00e4gelsbachstrasse 25, 91052 Erlangen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6536-4038","authenticated-orcid":false,"suffix":"Jr.","given":"David C","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, NC 27599, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2519-9984","authenticated-orcid":false,"given":"Mahdi","family":"Bagherpoor\u00a0Helabad","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery and Institute for Medical Physics and Biophysics, Leipzig University Medical School , 04103 Leipzig ,","place":["Germany"]},{"name":"Fachbereich Physik, Freie Universit\u00e4t Berlin , 14195 Berlin ,","place":["Germany"]},{"name":"Institute of Chemistry, Martin Luther-University Halle-Wittenberg , Weinbergweg 22, Halle (Saale) 06120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"2026101904331022400_B1","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1126\/science.aat6806","article-title":"Dynamic DNA methylation: in the right place at the right time","volume":"361","author":"Luo","year":"2018","journal-title":"Science"},{"key":"2026101904331022400_B2","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1111\/j.1399-0004.2011.01809.x","article-title":"Epigenetic modifications in cancer","volume":"81","author":"Kanwal","year":"2012","journal-title":"Clin Genet"},{"key":"2026101904331022400_B3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"2026101904331022400_B4","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature14192","article-title":"Function and information content of DNA methylation","volume":"517","author":"Sch\u00fcbeler","year":"2015","journal-title":"Nature"},{"key":"2026101904331022400_B5","doi-asserted-by":"publisher","first-page":"11799","DOI":"10.3390\/ijms150711799","article-title":"Base flip in DNA studied by molecular dynamics simulations of differently-oxidized forms of methyl-cytosine","volume":"15","author":"Bagherpoor\u00a0Helabad","year":"2014","journal-title":"Int J Mol Sci"},{"key":"2026101904331022400_B6","doi-asserted-by":"publisher","first-page":"1047896","DOI":"10.1155\/2020\/1047896","article-title":"Epigenetic clock: DNA methylation in aging","volume":"2020","author":"Jiang","year":"2020","journal-title":"Stem Cells Int"},{"key":"2026101904331022400_B7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.tig.2011.09.004","article-title":"De novo DNA methylation: a germ cell perspective","volume":"28","author":"Smallwood","year":"2012","journal-title":"Trends Genet"},{"key":"2026101904331022400_B8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41576-024-00760-8","article-title":"DNA methylation in mammalian development and disease","volume":"26","author":"Smith","year":"2025","journal-title":"Nat Rev Genet"},{"key":"2026101904331022400_B9","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.tig.2011.08.002","article-title":"Epigenetic factors influencing resistance to nuclear reprogramming","volume":"27","author":"Pasque","year":"2011","journal-title":"Trends Genet"},{"key":"2026101904331022400_B10","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1101\/gr.254904.119","article-title":"A comparison of gene expression and DNA methylation patterns across tissues and species","volume":"30","author":"Blake","year":"2020","journal-title":"Genome Res"},{"key":"2026101904331022400_B11","doi-asserted-by":"publisher","first-page":"e00726","DOI":"10.7554\/eLife.00726","article-title":"DNA methylation presents distinct binding sites for human transcription factors","volume":"2","author":"Hu","year":"2013","journal-title":"eLife"},{"key":"2026101904331022400_B12","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s00412-009-0221-9","article-title":"DNA methylation and methyl-CpG binding proteins: developmental requirements and function","volume":"118","author":"Bogdanovi\u0107","year":"2009","journal-title":"Chromosoma"},{"key":"2026101904331022400_B13","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.2217\/epi.15.39","article-title":"Methyl-CpG-binding domain proteins: readers of the epigenome","volume":"7","author":"Du","year":"2015","journal-title":"Epigenomics"},{"key":"2026101904331022400_B14","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1017\/S0016672398533307","article-title":"Identification and characterization of a family of mammalian methyl CpG-binding proteins","volume":"72","author":"Hendrich","year":"1998","journal-title":"Genet Res"},{"key":"2026101904331022400_B15","doi-asserted-by":"publisher","first-page":"7344","DOI":"10.1074\/jbc.RA118.001785","article-title":"Structural basis for the ability of MBD domains to bind methyl-CG and TG sites in DNAJ","volume":"293","author":"Liu","year":"2018","journal-title":"Biol Chem"},{"key":"2026101904331022400_B16","doi-asserted-by":"publisher","first-page":"3240","DOI":"10.1111\/febs.14850","article-title":"Structural analyses reveal that MBD3 is a methylated CG binder","volume":"286","author":"Liu","year":"2019","journal-title":"FEBS J"},{"key":"2026101904331022400_B17","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1016\/j.jmb.2019.10.007","article-title":"The methyl-CpG\u2013Binding domain 2 and 3 proteins and formation of the nucleosome remodeling and deacetylase complex","volume":"432","author":"Leighton","year":"2020","journal-title":"J Mol Biol"},{"key":"2026101904331022400_B18","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1074\/jbc.M113.512236","article-title":"Probing the dynamic distribution of bound states for methylcytosine-binding domains on DNAJ","volume":"289","author":"Cramer","year":"2014","journal-title":"Biol Chem"},{"key":"2026101904331022400_B19","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1101\/gad.13.15.1924","article-title":"Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation","volume":"13","author":"Zhang","year":"1999","journal-title":"Genes Dev"},{"key":"2026101904331022400_B20","doi-asserted-by":"publisher","first-page":"e21964","DOI":"10.7554\/eLife.21964","article-title":"DNA methylation directs genomic localization of MBD2 and MBD3 in embryonic stem cells","volume":"5","author":"Hainer","year":"2016","journal-title":"eLife"},{"key":"2026101904331022400_B21","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3389\/fgene.2016.00093","article-title":"Emerging molecular and biological functions of MBD2, a reader of DNA methylation","volume":"7","author":"Wood","year":"2016","journal-title":"Front Genet"},{"key":"2026101904331022400_B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jbc.2022.102428","article-title":"Densely methylated DNA traps methyl-CpG\u2013binding domain protein 2 but permits free diffusion by methyl-CpG\u2013binding domain protein 3","volume":"298","author":"Leighton","year":"2022","journal-title":"J Biol Chem"},{"key":"2026101904331022400_B23","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1158\/1541-7786.MCR-11-0252","article-title":"Methyl-binding domain protein 2\u2013dependent proliferation and survival of breast cancer cells","volume":"9","author":"Mian","year":"2011","journal-title":"Mol Cancer Res"},{"key":"2026101904331022400_B24","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1097\/CM9.0000000000002482","article-title":"Methyl CpG binding domain protein 2 (MBD2) in inflammation","volume":"135","author":"Lei","year":"2022","journal-title":"Chin Med J"},{"key":"2026101904331022400_B25","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41398-023-02561-9","article-title":"Methyl-CpG binding domain 2 (MBD2) is an epigenetic regulator of autism-risk genes and cognition","volume":"13","author":"Lax","year":"2023","journal-title":"Transl Psychiatry"},{"key":"2026101904331022400_B26","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.cell.2013.03.011","article-title":"Methylation-dependent and-independent genomic targeting principles of the MBD protein family","volume":"153","author":"Baubec","year":"2013","journal-title":"Cell"},{"key":"2026101904331022400_B27","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1093\/nar\/gkt035","article-title":"Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences","volume":"41","author":"G\u00fcnther","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B28","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.3324\/haematol.2018.210963","article-title":"Disruption of the MBD2-NuRD complex but not MBD3-NuRD induces high level HbF expression in human adult erythroid cells","volume":"104","author":"Yu","year":"2019","journal-title":"Haematologica"},{"key":"2026101904331022400_B29","doi-asserted-by":"publisher","first-page":"e2302254120","DOI":"10.1073\/pnas.2302254120","article-title":"MBD2a-NuRD binds to the methylated \u03b3-globin gene promoter and uniquely forms a complex required for silencing of HbF expression","volume":"120","author":"Shang","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101904331022400_B30","doi-asserted-by":"publisher","first-page":"12972","DOI":"10.1093\/nar\/gkaa1121","article-title":"The topology of chromatin-binding domains in the NuRD deacetylase complex","volume":"48","author":"Millard","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B31","doi-asserted-by":"publisher","first-page":"6741","DOI":"10.1093\/nar\/gkr262","article-title":"Solution structure and dynamic analysis of chicken MBD2 methyl binding domain bound to a target-methylated DNA sequence","volume":"39","author":"Scarsdale","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B32","doi-asserted-by":"publisher","first-page":"6653","DOI":"10.1093\/emboj\/18.23.6653","article-title":"Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1","volume":"18","author":"Ohki","year":"1999","journal-title":"EMBO J"},{"key":"2026101904331022400_B33","doi-asserted-by":"publisher","first-page":"3353","DOI":"10.1074\/jbc.M007224200","article-title":"DNA recognition by the methyl-CpG binding domain of MeCP2","volume":"276","author":"Free","year":"2001","journal-title":"J Biol Chem"},{"key":"2026101904331022400_B34","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1093\/hmg\/9.7.1119","article-title":"Long-read sequence analysis of the MeCP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location","volume":"9","author":"Cheadle","year":"2000","journal-title":"Hum Mol Genet"},{"key":"2026101904331022400_B35","doi-asserted-by":"publisher","first-page":"6357","DOI":"10.1021\/acs.biochem.5b00790","article-title":"Impact of Rett syndrome mutations on MeCP2 MBD stability","volume":"54","author":"Kucukkal","year":"2015","journal-title":"Biochemistry"},{"key":"2026101904331022400_B36","doi-asserted-by":"publisher","first-page":"11218","DOI":"10.1093\/nar\/gku782","article-title":"Solution structure and intramolecular exchange of methyl-cytosine binding domain protein 4 (MBD4) on DNA suggests a mechanism to scan for mCpG\/TpG mismatches","volume":"42","author":"Walavalkar","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B37","doi-asserted-by":"publisher","first-page":"9164","DOI":"10.1093\/nar\/gkx548","article-title":"CpG and methylation-dependent DNA binding and dynamics of the methylcytosine binding domain 2 protein at the single-molecule level","volume":"45","author":"Pan","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B38","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1021\/acs.jpcb.1c00757","article-title":"What are the molecular requirements for protein sliding along DNA?","volume":"125","author":"Bigman","year":"2021","journal-title":"J Phys Chem B"},{"key":"2026101904331022400_B39","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1038\/nsmb.1716","article-title":"Nonspecifically bound proteins spin while diffusing along DNA","volume":"16","author":"Blainey","year":"2009","journal-title":"Nat Struct Mol Biol"},{"key":"2026101904331022400_B40","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1038\/s41586-020-2413-7","article-title":"DNA surface exploration and operator bypassing during target search","volume":"583","author":"Marklund","year":"2020","journal-title":"Nature"},{"key":"2026101904331022400_B41","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1093\/nar\/gkx1220","article-title":"Energetic funnel facilitates facilitated diffusion","volume":"46","author":"Cencini","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B42","doi-asserted-by":"publisher","first-page":"5001","DOI":"10.1093\/nar\/gky208","article-title":"Sliding of a single lac repressor protein along DNA is tuned by DNA sequence and molecular switching","volume":"46","author":"Tempestini","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B43","doi-asserted-by":"publisher","first-page":"5381","DOI":"10.1038\/s41467-018-07797-4","article-title":"Breaking the speed limit with multimode fast scanning of DNA by Endonuclease V","volume":"9","author":"Ahmadi","year":"2018","journal-title":"Nat Commun"},{"key":"2026101904331022400_B44","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1093\/nar\/gkad068","article-title":"Target search by an imported conjugative DNA element for a unique integration site along a bacterial chromosome during horizontal gene transfer","volume":"51","author":"Arbel-Goren","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B45","doi-asserted-by":"publisher","first-page":"5530","DOI":"10.1093\/nar\/gkz308","article-title":"Quantifying the two-state facilitated diffusion model of protein\u2013DNA interactions","volume":"47","author":"Leven","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B46","doi-asserted-by":"publisher","first-page":"17957","DOI":"10.1073\/pnas.1109594108","article-title":"Frustration in protein\u2013DNA binding influences conformational switching and target search kinetics","volume":"108","author":"Marcovitz","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101904331022400_B47","doi-asserted-by":"publisher","first-page":"198101","DOI":"10.1103\/PhysRevLett.110.198101","article-title":"Distance matters: the impact of gene proximity in bacterial gene regulation","volume":"110","author":"Pulkkinen","year":"2013","journal-title":"Phys Rev Lett"},{"key":"2026101904331022400_B48","doi-asserted-by":"publisher","first-page":"033008","DOI":"10.1103\/PRXLife.2.033008","article-title":"Enhancer-insulator pairing reveals heterogeneous dynamics in long-distance 3D gene regulation","volume":"2","author":"Hedstr\u00f6m","year":"2024","journal-title":"PRX Life"},{"key":"2026101904331022400_B49","doi-asserted-by":"publisher","first-page":"19796","DOI":"10.1073\/pnas.1307905110","article-title":"Transcription-factor binding and sliding on DNA studied using micro-and macroscopic models","volume":"110","author":"Marklund","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101904331022400_B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep17107","article-title":"p53 dynamics upon response element recognition explored by molecular simulations","volume":"5","author":"Terakawa","year":"2015","journal-title":"Sci Rep"},{"key":"2026101904331022400_B51","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1002\/wcms.1262","article-title":"Coarse-grained models for studying protein diffusion along DNA. Wiley Interdiscip","volume":"6","author":"Bhattacherjee","year":"2016","journal-title":"Rev Comput Mol Sci"},{"key":"2026101904331022400_B52","doi-asserted-by":"publisher","first-page":"28527","DOI":"10.1039\/C7CP04380E","article-title":"Roles of conformational disorder and downhill folding in modulating protein\u2013DNA recognition","volume":"19","author":"Chu","year":"2017","journal-title":"Phys Chem Chem Phys"},{"key":"2026101904331022400_B53","doi-asserted-by":"publisher","first-page":"7643","DOI":"10.1093\/nar\/gkx534","article-title":"How proteins bind to DNA: target discrimination and dynamic sequence search by the telomeric protein TRF1","volume":"45","author":"Wiecz\u00f3r","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B54","doi-asserted-by":"publisher","first-page":"5967","DOI":"10.1002\/anie.201900935","article-title":"Atomic resolution insight into Sac7d protein binding to DNA and associated global changes by molecular dynamics simulations","volume":"58","author":"Zacharias","year":"2019","journal-title":"Angew Chem Int Ed"},{"key":"2026101904331022400_B55","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1093\/nar\/gkaa1252","article-title":"Atomic resolution of short-range sliding dynamics of thymine DNA glycosylase along DNA minor-groove for lesion recognition","volume":"49","author":"Tian","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B56","doi-asserted-by":"publisher","first-page":"e2102621118","DOI":"10.1073\/pnas.2102621118","article-title":"Revealing atomic-scale molecular diffusion of a plant-transcription factor WRKY domain protein along DNA","volume":"118","author":"Dai","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101904331022400_B57","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"2026101904331022400_B58","doi-asserted-by":"publisher","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","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"2026101904331022400_B59","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J Chem Theory Comput"},{"key":"2026101904331022400_B60","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nmeth.3658","article-title":"Parmbsc1: a refined force field for DNA simulations","volume":"13","author":"Ivani","year":"2016","journal-title":"Nat Methods"},{"key":"2026101904331022400_B61","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1093\/nar\/gky1237","article-title":"How methyl-sugar interactions determine DNA structure and flexibility","volume":"47","author":"Liebl","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B62","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.4161\/15592294.2014.988043","article-title":"Understanding the structural and dynamic consequences of DNA epigenetic modifications: Computational insights into cytosine methylation and hydroxymethylation","volume":"9","author":"Carvalho","year":"2014","journal-title":"Epigenetics"},{"key":"2026101904331022400_B63","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J Chem Phys"},{"key":"2026101904331022400_B64","doi-asserted-by":"publisher","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical sampling through velocity rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J Chem Phys"},{"key":"2026101904331022400_B65","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: a new molecular dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J Appl Phys"},{"key":"2026101904331022400_B66","doi-asserted-by":"publisher","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":"2026101904331022400_B67","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J Chem Phys"},{"key":"2026101904331022400_B68","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12&lt;1463::AID-JCC4&gt;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":"2026101904331022400_B69","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/s41592-019-0506-8","article-title":"Promoting transparency and reproducibility in enhanced molecular simulations","volume":"16","author":"PLUMED consortium.","year":"2019","journal-title":"Nat Methods"},{"key":"2026101904331022400_B70","doi-asserted-by":"publisher","first-page":"6358","DOI":"10.1073\/pnas.1303186110","article-title":"Funnel metadynamics as accurate binding free-energy method","volume":"110","author":"Limongelli","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101904331022400_B71","first-page":"8","article-title":"The PyMOL molecular graphics system","volume":"1","year":"2015","journal-title":"Version"},{"key":"2026101904331022400_B72","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1126\/science.271.5251.997","article-title":"Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture force","volume":"271","author":"Grubm\u00fcller","year":"1996","journal-title":"Science"},{"key":"2026101904331022400_B73","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: fast, flexible, and free","volume":"26","author":"Van\u00a0Der\u00a0Spoel","year":"2005","journal-title":"J Comput Chem"},{"key":"2026101904331022400_B74","doi-asserted-by":"publisher","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":"2026101904331022400_B75","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/0021-9991(77)90121-8","article-title":"Nonphysical sampling distributions in Monte Carlo free-energy estimation: umbrella sampling","volume":"23","author":"Torrie","year":"1977","journal-title":"J Comput Phys"},{"key":"2026101904331022400_B76","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1002\/jcc.540130812","article-title":"The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method","volume":"13","author":"Kumar","year":"1992","journal-title":"J Comput Chem"},{"key":"2026101904331022400_B77","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/S0010-4655(00)00215-0","article-title":"Extension to the weighted histogram analysis method: combining umbrella sampling with free energy calculations","volume":"135","author":"Souaille","year":"2001","journal-title":"Comput Phys Commun"},{"key":"2026101904331022400_B78","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1093\/nar\/gkv168","article-title":"An intrinsically disordered region of methyl-CpG binding domain protein 2 (MBD2) recruits the histone deacetylase core of the NuRD complex","volume":"43","author":"Desai","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B79","doi-asserted-by":"publisher","first-page":"25191","DOI":"10.1074\/jbc.M302677200","article-title":"Solution structure of the phosphoryl transfer complex between the signal-transducing protein IIAGlucose and the cytoplasmic domain of the glucose transporter IICBGlucose of the Escherichia coli glucose phosphotransferase system","volume":"278","author":"Cai","year":"2003","journal-title":"J Biol Chem"},{"key":"2026101904331022400_B80","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/BF00197809","article-title":"NMRPipe: a multidimensional spectral processing system based on UNIX pipes","volume":"6","author":"Delaglio","year":"1995","journal-title":"J Biomol NMR"},{"key":"2026101904331022400_B81","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1002\/prot.20449","article-title":"The CCPN data model for NMR spectroscopy: development of a software pipeline","volume":"59","author":"Vranken","year":"2005","journal-title":"Proteins"},{"key":"2026101904331022400_B82","doi-asserted-by":"publisher","first-page":"17874","DOI":"10.1073\/pnas.1311599110","article-title":"Native contacts determine protein folding mechanisms in atomistic simulations","volume":"110","author":"Best","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101904331022400_B83","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1002\/(SICI)1521-3773(19990115)38:1\/2&lt;236::AID-ANIE236&gt;3.0.CO;2-M","article-title":"Peptide folding: when simulation meets experiment","volume":"38","author":"Daura","year":"1999","journal-title":"Angew Chem Int Ed"},{"key":"2026101904331022400_B84","doi-asserted-by":"publisher","first-page":"031910","DOI":"10.1103\/PhysRevE.65.031910","article-title":"Convergence of sampling in protein simulations","volume":"65","author":"Hess","year":"2002","journal-title":"Phys Rev E"},{"key":"2026101904331022400_B85","doi-asserted-by":"publisher","first-page":"5917","DOI":"10.1093\/nar\/gkp608","article-title":"Conformational analysis of nucleic acids revisited: curves","volume":"37","author":"Lavery","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B86","doi-asserted-by":"publisher","first-page":"W68","DOI":"10.1093\/nar\/gkr316","article-title":"CURVES+ web server for analyzing and visualizing the helical, backbone and groove parameters of nucleic acid structures","volume":"39","author":"Blanchet","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B87","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/jcc.540160303","article-title":"The double cubic lattice method: efficient approaches to numerical integration of surface area and volume and to dot surface contouring of molecular assemblies","volume":"16","author":"Eisenhaber","year":"1995","journal-title":"J Comput Chem"},{"key":"2026101904331022400_B88","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/bip.10528","article-title":"DNA fine structure and dynamics in crystals and in solution: the impact of BI\/BII backbone conformations","volume":"73","author":"Djuranovic","year":"2004","journal-title":"Biopolymers"},{"key":"2026101904331022400_B89","doi-asserted-by":"publisher","first-page":"9170","DOI":"10.1021\/ja061686j","article-title":"Quantification of DNA BI\/BII backbone states in solution. Implications for DNA overall structure and recognition","volume":"128","author":"Heddi","year":"2006","journal-title":"J Am Chem Soc"},{"key":"2026101904331022400_B90","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1021\/jp711203m","article-title":"31P NMR investigation of backbone dynamics in DNA binding sites","volume":"113","author":"Tian","year":"2009","journal-title":"J Phys Chem B"},{"key":"2026101904331022400_B91","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1021\/acs.biochem.0c00784","article-title":"Single-base lesions and mismatches alter the backbone conformational dynamics in DNA","volume":"60","author":"Westwood","year":"2021","journal-title":"Biochemistry"},{"key":"2026101904331022400_B92","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1021\/acs.biochem.3c00230","article-title":"Backbone conformational equilibrium in mismatched DNA correlates with enzyme activity","volume":"62","author":"Westwood","year":"2023","journal-title":"Biochemistry"},{"key":"2026101904331022400_B93","doi-asserted-by":"publisher","first-page":"4473","DOI":"10.1021\/acs.jctc.5b00508","article-title":"Differential deformability of the DNA minor groove and altered BI\/BII backbone conformational equilibrium by the monovalent ions Li+, Na+, K+, and Rb+ via water-mediated hydrogen bonding","volume":"11","author":"Savelyev","year":"2015","journal-title":"J Chem Theory Comput"},{"key":"2026101904331022400_B94","doi-asserted-by":"publisher","first-page":"17139","DOI":"10.1021\/ja104564g","article-title":"Phosphorus chemical shifts in a nucleic acid backbone from combined molecular dynamics and density functional calculations","volume":"132","author":"Precechtelov\u00e1","year":"2010","journal-title":"J Am Chem Soc"},{"key":"2026101904331022400_B95","doi-asserted-by":"publisher","first-page":"40674","DOI":"10.1038\/srep40674","article-title":"Methylation specific targeting of a chromatin remodeling complex from sponges to humans","volume":"7","author":"Cramer","year":"2017","journal-title":"Sci Rep"},{"key":"2026101904331022400_B96","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1016\/j.jmb.2017.04.009","article-title":"Structural basis of MeCP2 distribution on non-CpG methylated and hydroxymethylated DNAJ","volume":"429","author":"Sperlazza","year":"2017","journal-title":"Mol Biol"},{"key":"2026101904331022400_B97","doi-asserted-by":"publisher","first-page":"14402","DOI":"10.1074\/jbc.M705007200","article-title":"Importance of hydrogen bonding for efficiency and specificity of the human mitochondrial DNA polymerase","volume":"283","author":"Lee","year":"2008","journal-title":"J Biol Chem"},{"key":"2026101904331022400_B98","doi-asserted-by":"publisher","first-page":"11568","DOI":"10.1021\/bi026937p","article-title":"Energetics of sequence-specific protein\u2013DNA association: computational analysis of integrase Tn916 binding to its target DNA","volume":"42","author":"Gorfe","year":"2003","journal-title":"Biochemistry"},{"key":"2026101904331022400_B99","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.pharmthera.2017.11.002","article-title":"Readers of DNA methylation, the MBD family as potential therapeutic targets","volume":"184","author":"Ginder","year":"2018","journal-title":"Pharmacol Ther"},{"key":"2026101904331022400_B100","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1146\/annurev-biochem-060408-091030","article-title":"Origins of specificity in protein\u2013DNA recognition","volume":"79","author":"Rohs","year":"2010","journal-title":"Annu Rev Biochem"},{"key":"2026101904331022400_B101","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cels.2018.12.001","article-title":"A de novo shape motif discovery algorithm reveals preferences of transcription factors for DNA shape beyond sequence motifs","volume":"8","author":"Samee","year":"2019","journal-title":"Cell Syst"},{"key":"2026101904331022400_B102","doi-asserted-by":"publisher","first-page":"2640","DOI":"10.1021\/jacsau.4c00393","article-title":"Role of shape deformation of DNA-binding sites in regulating the efficiency and specificity in their recognition by DNA-binding proteins","volume":"4","author":"Mishra","year":"2024","journal-title":"JACS Au"},{"key":"2026101904331022400_B103","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.1021\/acschembio.6b00450","article-title":"Binding analysis of methyl-CpG binding domain of MeCP2 and Rett syndrome mutations","volume":"11","author":"Yang","year":"2016","journal-title":"ACS Chem Biol"},{"key":"2026101904331022400_B104","doi-asserted-by":"publisher","first-page":"2101383","DOI":"10.1002\/advs.202101383","article-title":"Complete mapping of DNA\u2013protein interactions at the single-molecule level","volume":"8","author":"Liu","year":"2021","journal-title":"Adv Sci"},{"key":"2026101904331022400_B105","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1021\/bi00124a006","article-title":"Effects of temperature on protein structure and dynamics: X-ray crystallographic studies of the protein ribonuclease-A at nine different temperatures from 98 to 320K","volume":"31","author":"Tilton","year":"1992","journal-title":"Biochemistry"},{"key":"2026101904331022400_B106","doi-asserted-by":"publisher","first-page":"16247","DOI":"10.1073\/pnas.1111325108","article-title":"Accessing protein conformational ensembles using room-temperature X-ray crystallography","volume":"108","author":"Fraser","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101904331022400_B107","doi-asserted-by":"publisher","first-page":"2401838","DOI":"10.1002\/advs.202401838","article-title":"Sodium ion-induced structural transition on the surface of a DNA-interacting protein","volume":"11","author":"Xu","year":"2024","journal-title":"Adv Sci"},{"key":"2026101904331022400_B108","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1093\/nar\/gkv080","article-title":"Analyzing ion distributions around DNA: sequence-dependence of potassium ion distributions from microsecond molecular dynamics","volume":"43","author":"Pasi","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026101904331022400_B109","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1021\/acs.accounts.0c00212","article-title":"Dynamics of ionic interactions at protein\u2013nucleic acid interfaces","volume":"53","author":"Yu","year":"2020","journal-title":"Acc Chem Res"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/19\/gkag952\/72085464\/gkag952.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/19\/gkag952\/72085464\/gkag952.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T08:33:20Z","timestamp":1792398800000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/doi\/10.1093\/nar\/gkag952\/8937190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":109,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkag952","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10,28]]},"published":{"date-parts":[[2026,10,13]]},"article-number":"gkag952"}}