{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T05:26:43Z","timestamp":1735968403117,"version":"3.32.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91953101"],"award-info":[{"award-number":["91953101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Quant. Biol."],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>N<jats:sup>6<\/jats:sup>\u2010methyl adenosine (m<jats:sup>6<\/jats:sup>A) modifications of mRNA and long non\u2010coding RNA (lncRNAs) are known to play a significant role in regulation of gene expression and organismal development. Besides writer and eraser proteins of this dynamic modification, the YT521\u2010B homology (YTH) domain can recognize the modification involved in numerous cellular processes. The function of proteins containing YTH domain and its binding mode with N<jats:sup>6<\/jats:sup>\u2010Methyladenosine RNA has attracted considerable attention. However, the structural and dynamic characteristics of the YTH domain in complex with m<jats:sup>6<\/jats:sup>A RNA is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This work presents results of accelerated molecular dynamics (aMD) simulations at the timescale of microseconds. Principal component analysis (PCA), molecular mechanics generalized Born surface area (MM\/GBSA) calculations, contact analysis and contact\u2010based principal component analysis (conPCA) provide new insights into structure and dynamics of the YTH\u2010RNA complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The aMD simulations indicate that the recognition loop has a larger movement away from the binding pocket in the YTH\u2010A3 RNA than that in the YTH\u2010m<jats:sup>6<\/jats:sup>A3 RNA. In aMD trajectories of the apo YTH, there is a significant close\u2010open transition of the recognition loop, that is to say, the apo YTH can take both the closed and open structure. We have found that the YTH domain binds more favorably to the methylated RNA than the non\u2010methylated RNA. The per\u2010residue free energy decomposition and conPCA suggest that hydrophobic residues including W380, L383\u2010V385, W431\u2010P434, M437, and M441\u2010L442, may play important roles in favorable binding of the m<jats:sup>6<\/jats:sup>A RNA to the YTH domain, which is also supported by aMD simulations of a double mutated system (L383A\/M437A).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results are in good agreement with higher structural stability of the YTH\u2010m<jats:sup>6<\/jats:sup>A RNA than that of the YTH\u2010A3 RNA. The addition of a methylation group on A3 can enhance its binding to the hydrophobic pocket in the YTH domain. Our simulations support a \u2018conformational selection\u2019 mechanism between the YTH\u2010RNA binding. This work may aid in our understanding of the structural and dynamic characteristics of the YTH protein in complex with the methylated RNA.<\/jats:p><\/jats:sec>","DOI":"10.15302\/j-qb-022-0297","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T08:31:14Z","timestamp":1679473874000},"page":"72-81","source":"Crossref","is-referenced-by-count":1,"title":["Structural and dynamic properties of the YTH domain in complex with N<sup>6<\/sup>\u2010methyladenosine RNA studied by accelerated molecular dynamics simulations"],"prefix":"10.1002","volume":"11","author":[{"given":"Mingwei","family":"Li","sequence":"first","affiliation":[{"name":"<!--1--> MOE Key Laboratory for Membraneless Organelles &amp; Cellular Dynamics National Science Center for Physical Sciences at Microscale Division of Life Sciences and Medicine, and Biomedical Sciences and Health Laboratory of Anhui Province University of Science and Technology of China Hefei 230026 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanglin","family":"Chen","sequence":"additional","affiliation":[{"name":"<!--2--> Department of Physics University of Science and Technology of China Hefei 230026 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"<!--1--> MOE Key Laboratory for Membraneless Organelles &amp; Cellular Dynamics National Science Center for Physical Sciences at Microscale Division of Life Sciences and Medicine, and Biomedical Sciences and Health Laboratory of Anhui Province University of Science and Technology of China Hefei 230026 China"},{"name":"<!--2--> Department of Physics University of Science and Technology of China Hefei 230026 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3785"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3724"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.003"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11112"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx141"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12730"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elu039"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1432"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.005"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.687"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku085"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.014"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15377"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.104711"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.99"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169\u2010328X(97)00262\u20103"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.11.3909"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1116"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412742111"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1654"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13072\u2010020\u201000355\u20107"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.153"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.680389"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.0c01136"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.0c01029"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340170408"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959\u2010440X(00)00061\u20100"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct300418h"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.4938249"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.44.2.98"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/79575"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2020.01.006"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010\u20104655(95)00041\u2010D"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20290"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00255"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00124a002"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct200162x"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct600329w"},{"key":"e_1_2_8_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp003020w"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/00268978800101881"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.470648"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096\u2010987X(20000130)21:2<157::AID\u2010JCC7>3.0.CO;2\u20102"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1755656"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar000033j"},{"key":"e_1_2_8_47_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008763014207"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt055"}],"container-title":["Quantitative 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