{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:24:05Z","timestamp":1767612245981,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The Kv1.2 channel plays an important role in the maintenance of resting membrane potential and the regulation of the cellular excitability of neurons, whose silencing or mutations can elicit neuropathic pain or neurological diseases (e.g., epilepsy and ataxia). Scorpion venom contains a variety of peptide toxins targeting the pore region of this channel. Despite a large amount of structural and functional data currently available, their detailed interaction modes are poorly understood. In this work, we choose four Kv1.2-targeted scorpion toxins (Margatoxin, Agitoxin-2, OsK-1, and Mesomartoxin) to construct their complexes with Kv1.2 based on the experimental structure of ChTx-Kv1.2. Molecular dynamics simulation of these complexes lead to the identification of hydrophobic patches, hydrogen-bonds, and salt bridges as three essential forces mediating the interactions between this channel and the toxins, in which four Kv1.2-specific interacting amino acids (D353, Q358, V381, and T383) are identified for the first time. This discovery might help design highly selective Kv1.2-channel inhibitors by altering amino acids of these toxins binding to the four channel residues. Finally, our results provide new evidence in favor of an induced fit model between scorpion toxins and K+ channel interactions.<\/jats:p>","DOI":"10.3390\/toxins9110354","type":"journal-article","created":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T16:01:19Z","timestamp":1509552079000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular Dynamics Simulation Reveals Specific Interaction Sites between Scorpion Toxins and Kv1.2 Channel: Implications for Design of Highly Selective Drugs"],"prefix":"10.3390","volume":"9","author":[{"given":"Shouli","family":"Yuan","sequence":"first","affiliation":[{"name":"Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0614-9207","authenticated-orcid":false,"given":"Shunyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11352","DOI":"10.1073\/pnas.1000142107","article-title":"Structure of the full-length Shaker potassium channel Kv1.2 by normal-mode-based X-ray crystallographic refinement","volume":"107","author":"Chen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nrd2983","article-title":"Voltage-gated potassium channels as therapeutic targets","volume":"8","author":"Wulff","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cremonez, C.M., Maiti, M., Peigneur, S., Cassoli, J.S., Dutra, A.A., Waelkens, E., Lescrinier, E., Herdewijn, P., de Lima, M.E., and Pimenta, A.M. (2016). Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins. Toxins (Basel), 8.","DOI":"10.3390\/toxins8100288"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32160","DOI":"10.1074\/jbc.M110.153676","article-title":"A new Kv1.2 channelopathy underlying cerebellar ataxia","volume":"285","author":"Xie","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1152\/jn.00640.2006","article-title":"Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons","volume":"98","author":"Brew","year":"2007","journal-title":"J. Neurophysiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1111\/cge.12542","article-title":"Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: Proposal for a new channelopathy","volume":"87","author":"Pena","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng.3239","article-title":"De-novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy","volume":"47","author":"Syrbe","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22211","DOI":"10.1073\/pnas.0910123106","article-title":"A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library","volume":"106","author":"Takacs","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.peptides.2015.06.004","article-title":"Isolation and characterization of Ts19 Fragment II, a new long chain potassium channel toxinfrom Tityus serrulatus venom","volume":"80","author":"Cerni","year":"2016","journal-title":"Peptides"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13813","DOI":"10.1074\/jbc.M112.343996","article-title":"Hg1, novel peptide inhibitor specific for Kv1.3 channels from first scorpion Kunitz-type potassium channel toxin family","volume":"287","author":"Chen","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Moreels, L., Peigneur, S., Yamaguchi, Y., Vriens, K., Waelkens, E., Zhu, S., Thevissen, K., Cammue, B.P., Sato, K., and Tytgat, J. (2016). Expanding the pharmacological profile of \u03ba-hefutoxin 1 and analogues: A focus on the inhibitory effect on the oncogenic channel Kv10.1. Peptides.","DOI":"10.1016\/j.peptides.2016.08.008"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/jbt.20382","article-title":"ImKTx1, a new Kv1.3 channel blocker with a unique primary structure","volume":"25","author":"Chen","year":"2011","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bcp.2014.12.002","article-title":"Mesomartoxin, a new Kv1.2-selective scorpion toxin interacting with the channel selectivity filter","volume":"93","author":"Wang","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1042\/BJ20041379","article-title":"K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpionvenom","volume":"385","author":"Mouhat","year":"2005","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.toxicon.2014.05.002","article-title":"Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels","volume":"87","author":"Bartok","year":"2014","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1110\/ps.073122908","article-title":"Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX chimera, a new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion toxins","volume":"17","author":"Pimentel","year":"2008","journal-title":"Protein Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0896-6273(00)80030-6","article-title":"Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis","volume":"16","author":"Ranganathan","year":"1996","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00594","DOI":"10.7554\/eLife.00594","article-title":"Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel","volume":"2","author":"Banerjee","year":"2013","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.32607\/20758251-2016-8-2-35-46","article-title":"Modeling of the binding of peptide blockers to voltage-gated potassium channels: Approaches and evidence","volume":"8","author":"Novoseletsky","year":"2016","journal-title":"Acta Nat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/prot.21706","article-title":"Molecular basis of inhibitory peptide maurotoxin recognizing Kv1.2 channel explored by ZDOCK and molecular dynamic simulations","volume":"70","author":"Yi","year":"2008","journal-title":"Proteins"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chen, R., and Chung, S.H. (2012). Structural basis of the selective block of Kv1.2 by maurotoxin from computer simulations. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047253"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00894-015-2822-y","article-title":"Scorpion toxins prefer salt solutions","volume":"21","author":"Nikouee","year":"2015","journal-title":"J. Mol. Model."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7749","DOI":"10.1021\/bi00149a002","article-title":"Mapping function to structure in a channel-blocking peptide: Electrostatic mutants of charybdotoxin","volume":"31","author":"Park","year":"1992","journal-title":"Biochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0896-6273(92)90169-E","article-title":"Interaction of charybdotoxin with permeant ions inside the pore of a K+ channel","volume":"9","author":"Park","year":"1992","journal-title":"Neuron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/nature04649","article-title":"Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR","volume":"440","author":"Lange","year":"2006","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/molbev\/msu038","article-title":"Experimental conversion of a defensin into a neurotoxin: Implications for origin of toxic function","volume":"31","author":"Zhu","year":"2014","journal-title":"Mol. Biol. Evol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6404","DOI":"10.1073\/pnas.92.14.6404","article-title":"Scorpion toxins as natural scaffolds for protein engineering","volume":"92","author":"Vita","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11488","DOI":"10.1021\/bi026136m","article-title":"Role of disulfide bonds in folding and activity of leiurotoxin I: Just two disulfides suffice","volume":"41","author":"Zhu","year":"2002","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lee, C.W., Wang, H.J., Hwang, J.W., and Tseng, C.P. (2014). Protein thermal stability enhancement by designing salt bridges: A combined computational and experimental study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112751"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.bbrc.2008.09.033","article-title":"A new Kaliotoxin selective towards Kv1.3 and Kv1.2 but not Kv1.1 channels expressed in oocytes","volume":"376","author":"Abbas","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ye, F., Hu, Y., Yu, W., Xie, Z., Hu, J., Cao, Z., Li, W., and Wu, Y. (2016). The scorpion toxin analogue BmKTX-D33H as a potential Kv1.3 channel-selective immunomodulator for autoimmune diseases. Toxins (Basel), 8.","DOI":"10.3390\/toxins8040115"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1016\/j.bpj.2011.10.029","article-title":"Modeling the binding of three toxins to the voltage-gated potassium channel (Kv1.3)","volume":"101","author":"Chen","year":"2011","journal-title":"Biophys. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.toxicon.2012.03.022","article-title":"Mapping of scorpion toxin receptor sites at voltage-gated sodium channels","volume":"60","author":"Gurevitz","year":"2012","journal-title":"Toxicon"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1529\/biophysj.103.039461","article-title":"Computational simulations of interactions of scorpion toxins with the voltage-gated potassium ion channel","volume":"86","author":"Yu","year":"2004","journal-title":"Biophys. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.bcp.2008.08.018","article-title":"A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus","volume":"76","author":"Corzo","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.bbapap.2017.02.001","article-title":"C-Terminal residues in small potassium channel blockers OdK1 and OSK3 from scorpion venom fine-tune the selectivity","volume":"1865","author":"Kuzmenkov","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1042\/BJ20041705","article-title":"An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis","volume":"388","author":"Chagot","year":"2005","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/S0026-895X(25)10594-4","article-title":"Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines","volume":"45","author":"Grissmer","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1021\/pr060368g","article-title":"Interaction simulation of hERG K+ channel with its specific BeKm-1 peptide: Insight into the selectivity of molecular recognition","volume":"6","author":"Yi","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6807-11-3","article-title":"Differential molecular information of maurotoxin peptide recognizing IK(Ca) and Kv1.2 channels explored by computational simulation","volume":"11","author":"Yi","year":"2011","journal-title":"BMC Struct. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.toxicon.2015.04.018","article-title":"Solid phase synthesis, NMR structure determination of \u03b1-KTx3.8, its in silico docking to Kv1.x potassium channels, and electrophysiological analysis provide insights into toxin-channel selectivity","volume":"101","author":"Koha","year":"2015","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s11481-016-9710-9","article-title":"Complexes of peptide blockers with Kv1.6 pore domain: Molecular modeling and studies with KcsA-Kv1.6 channel","volume":"12","author":"Nekrasova","year":"2017","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jp003919d","article-title":"Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides","volume":"105","author":"Kaminski","year":"2001","journal-title":"J. Phys. Chem. B"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6269","DOI":"10.1021\/j100308a038","article-title":"The missing term in effective pair potentials","volume":"91","author":"Berendsen","year":"1987","journal-title":"J. Phys. Chem."},{"key":"ref_47","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":"ref_48","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.toxicon.2004.03.024","article-title":"Toxin determinants required for interaction with voltage-gated K1 channels","volume":"43","author":"Jouirou","year":"2004","journal-title":"Toxicon"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.toxicon.2003.11.029","article-title":"Molecular basis of alpha-KTx specificity","volume":"43","author":"Giangiacomo","year":"2004","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/0896-6273(95)90104-3","article-title":"Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxins","volume":"15","author":"Aiyar","year":"1995","journal-title":"Neuron"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0896-6273(00)80057-4","article-title":"Agitoxin footprinting the shaker potassium channel pore","volume":"16","author":"Gross","year":"1996","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1002\/prot.21833","article-title":"The investigation of interactions of kappa-Hefutoxin1 with the voltage-gated potassium channels: A computational simulation","volume":"71","author":"Zarrabi","year":"2008","journal-title":"Proteins"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1529\/biophysj.103.039156","article-title":"Simulation of the interaction between ScyTx and small conductance calcium-activated potassium channel by docking and MM-PBSA","volume":"87","author":"Wu","year":"2004","journal-title":"Biophys. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1021\/ci900025n","article-title":"Molecular information of charybdotoxin blockade in the large conductance calcium-activated potassium channel","volume":"49","author":"Qiu","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19058","DOI":"10.1074\/jbc.M802054200","article-title":"Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease","volume":"283","author":"Han","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.1021\/pr800494a","article-title":"Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1.1 and Kv1.3 channels","volume":"7","author":"Yin","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/S0006-3495(01)76138-3","article-title":"Brownian dynamics simulations of interaction between scorpion toxin Lq2 and potassium ion channel","volume":"80","author":"Cui","year":"2001","journal-title":"Biophys. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0022-2836(02)00095-5","article-title":"Brownian dynamic simulations of the recognition of the scorpion toxin P05 with the small-conductance calcium-activated potassium channels","volume":"318","author":"Cui","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1016\/S0006-3495(02)75270-3","article-title":"Modeling the structure of agitoxin in complex with the Shaker K+ channel: A computational approach based on the experimental distance restraints extracted from thermodynamic mutant cycles","volume":"83","author":"Eriksson","year":"2002","journal-title":"Biophys. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.sbi.2014.11.005","article-title":"Allostery without a conformational change? Revisiting the paradigm","volume":"30","author":"Nussinov","year":"2015","journal-title":"Curr. Opin. Struct. Biol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/11\/354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:49:07Z","timestamp":1760208547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/11\/354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,1]]},"references-count":61,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["toxins9110354"],"URL":"https:\/\/doi.org\/10.3390\/toxins9110354","relation":{},"ISSN":["2072-6651"],"issn-type":[{"type":"electronic","value":"2072-6651"}],"subject":[],"published":{"date-parts":[[2017,11,1]]}}}