{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:52:07Z","timestamp":1791197527955,"version":"4.1.0"},"reference-count":126,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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>Small peptides isolated from the venom of animals are potential scaffolds for ion channel drug discovery. This review article mainly focuses on the computational studies that have advanced our understanding of how various toxins interfere with the function of K+ channels. We introduce the computational tools available for the study of toxin-channel interactions. We then discuss how these computational tools have been fruitfully applied to elucidate the mechanisms of action of a wide range of venom peptides from scorpions, spiders, and sea anemone.<\/jats:p>","DOI":"10.3390\/toxins7124877","type":"journal-article","created":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T10:26:58Z","timestamp":1448965618000},"page":"5194-5211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Computational Studies of Venom Peptides Targeting Potassium Channels"],"prefix":"10.3390","volume":"7","author":[{"given":"Rong","family":"Chen","sequence":"first","affiliation":[{"name":"Research School of Biology, Australian National University, Acton ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Ho","family":"Chung","sequence":"additional","affiliation":[{"name":"Research School of Biology, Australian National University, Acton ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1021\/jm3011433","article-title":"Ion channels as therapeutic targets: A drug discovery perspective","volume":"56","author":"Bagal","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_2","first-page":"253","article-title":"Targeting ion channels for drug discovery","volume":"9","author":"Clare","year":"2010","journal-title":"Discov. Med."},{"key":"ref_3","first-page":"31","article-title":"Ion channel drug discovery expands into new disease areas","volume":"31","author":"Xie","year":"2004","journal-title":"Curr. Drug Discov."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1126\/science.8085162","article-title":"Molecular determinants of state-dependent block of Na+ channels by local anesthetics","volume":"265","author":"Ragsdale","year":"1994","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.tips.2004.03.010","article-title":"K+ channels as targets for specific immunomodulation","volume":"25","author":"Chandy","year":"2004","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.3390\/molecules15042825","article-title":"\u00b5-Conotoxins as leads in the development of new analgesics","volume":"15","author":"Norton","year":"2010","journal-title":"Molecules"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.3390\/toxins4111236","article-title":"Conotoxins targeting neuronal voltage-gated sodium channel subtypes: Potential analgesics?","volume":"4","author":"Knapp","year":"2012","journal-title":"Toxins"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1039\/B603083C","article-title":"Spider venoms: A rich source of acylpolyamines and peptides as new leads for CNS drugs","volume":"24","author":"Estrada","year":"2007","journal-title":"Nat. Prod. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1091\/mbc.8.11.2101","article-title":"Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology","volume":"8","author":"Olivera","year":"1997","journal-title":"Mol. Biol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.toxicon.2014.11.233","article-title":"Scorpion venom components as potential candidates for drug development","volume":"93","author":"Ortiz","year":"2015","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35335","DOI":"10.1074\/jbc.M002252200","article-title":"Novel \u03c9-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes","volume":"275","author":"Lewis","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1111\/bph.13081","article-title":"Seven novel modulators of the analgesic target NaV1.7 uncovered using a high-throughput venom-based discovery approach","volume":"172","author":"Klint","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35209","DOI":"10.1074\/jbc.M111.259507","article-title":"Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion \u03b1-toxins on sodium channels","volume":"286","author":"Gur","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"30719","DOI":"10.1074\/jbc.M112.370742","article-title":"Mapping the interaction site for a \u03b2-scorpion toxin in the pore module of domain III of voltage-gated Na+ channels","volume":"287","author":"Zhang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15426","DOI":"10.1073\/pnas.1112320108","article-title":"Mapping the receptor site for \u03b1-scorpion toxins on a Na+ channel voltage sensor","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1046\/j.1432-1327.1999.00625.x","article-title":"Scorpion toxins specific for Na+-channels","volume":"264","author":"Possani","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.toxicon.2006.09.023","article-title":"Voltage-gated sodium channel modulation by scorpion \u03b1-toxins","volume":"49","author":"Bosmans","year":"2007","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.2174\/0929867043363820","article-title":"Dendrotoxins: Structure-activity relationships and effects on potassium ion channels","volume":"11","author":"Harvey","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.toxicon.2011.03.017","article-title":"From snake venom toxins to therapeutics\u2014Cardiovascular examples","volume":"59","author":"Koh","year":"2012","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.toxicon.2013.05.022","article-title":"Cloning and characterization of a novel Kunitz-type inhibitor from scorpion with unique cysteine framework","volume":"72","author":"Chen","year":"2013","journal-title":"Toxicon"},{"key":"ref_24","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_25","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_26","doi-asserted-by":"crossref","first-page":"e35154","DOI":"10.1371\/journal.pone.0035154","article-title":"Structural and functional diversity of acidic scorpion potassium channel toxins","volume":"7","author":"Chen","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1021\/pr100027k","article-title":"Protein-protein recognition control by modulating electrostatic interactions","volume":"9","author":"Han","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_28","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_29","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: Insights into the selectivity of molecular recognition","volume":"6","author":"Yi","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1472-6807-11-3","article-title":"Differential molecular information of maurotoxin peptide recognizing IKCa and Kv1.2 channels explored by computational simulation","volume":"11","author":"Yi","year":"2011","journal-title":"BMC Struct. Biol."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1152\/physrev.00035.2012","article-title":"Computational methods of studying the binding of toxins from venomous animals to biological ion channels: Theory and applications","volume":"93","author":"Gordon","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"848","DOI":"10.3390\/md11030848","article-title":"Computational studies of marine toxins targeting ion channels","volume":"11","author":"Rashid","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.4155\/fmc.14.98","article-title":"Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics","volume":"6","author":"Kuyucak","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.280.5360.69","article-title":"The structure of the potassium channel: Molecular basis of K+ conduction and selectivity","volume":"280","author":"Doyle","year":"1998","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/417515a","article-title":"Crystal structure and mechanism of a calcium-gated potassium channel","volume":"417","author":"Jiang","year":"2002","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nature01580","article-title":"X-ray structure of a voltage-dependent K+ channel","volume":"423","author":"Jiang","year":"2003","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1126\/science.1116270","article-title":"Voltage sensor of Kv1.2: Structural basis of electromechanical coupling","volume":"309","author":"Long","year":"2005","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.1180310","article-title":"Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 \u00c5 resolution","volume":"326","author":"Tao","year":"2009","journal-title":"Science"},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature06265","article-title":"Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment","volume":"450","author":"Long","year":"2007","journal-title":"Nature"},{"key":"ref_42","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_43","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 experimental distance restraints extracted from thermodynamic mutant cycles","volume":"83","author":"Eriksson","year":"2002","journal-title":"Biophys. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.jmb.2007.07.050","article-title":"Protein-protein docking with backbone flexibility","volume":"373","author":"Wang","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.3390\/ijms11083016","article-title":"Advances and challenges in protein-ligand docking","volume":"11","author":"Huang","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1002\/anie.200502655","article-title":"Biomolecular modeling: Goals, problems, perspectives","volume":"45","author":"Bakowies","year":"2006","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1073\/pnas.2635314100","article-title":"Energetics of ion conduction through the gramicidin channel","volume":"101","author":"Allen","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1103\/PhysRevLett.78.2690","article-title":"Nonequilibrium equality for free energy differences","volume":"78","author":"Jarzynski","year":"1997","journal-title":"Phys. Rev. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"155104","DOI":"10.1063\/1.2904461","article-title":"Potential of mean force calculations of ligand binding to ion channels from Jarzynski\u2018s equality and umbrella sampling","volume":"128","author":"Chen","year":"2008","journal-title":"J. Chem. Phys."},{"key":"ref_50","doi-asserted-by":"crossref","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":"ref_51","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1085\/jgp.91.3.317","article-title":"Charybdotoxin block of single Ca2+-activated K+ channels. Effects of channel gating, voltage, and ionic strength","volume":"91","author":"Anderson","year":"1988","journal-title":"J. Gen. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1432-1033.1996.0491r.x","article-title":"Chemical synthesis and characterization of maurotoxin, a short scorpion toxin with four disulfide bridges that acts on K+ channels","volume":"242","author":"Kharrat","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18866","DOI":"10.1016\/S0021-9258(17)46707-X","article-title":"Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides Margaritatus venom that selectively inhibits voltage-dependent potassium channels","volume":"268","author":"Garciacalvo","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_54","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 scorpion venom","volume":"385","author":"Mouhat","year":"2005","journal-title":"Biochem. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.bcp.2004.10.018","article-title":"Assignment of voltage-gated potassium channel blocking activity to \u03ba-KTx1.3, a non-toxic homologue of \u03ba-hefutoxin-1, from Heterometrus spinifer venom","volume":"69","author":"Nirthanan","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1126\/science.1720574","article-title":"Refined structure of charybdotoxin: Common motifs in scorpion toxins and insect defensins","volume":"254","author":"Bontems","year":"1991","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/(SICI)1097-0134(199711)29:3<321::AID-PROT6>3.0.CO;2-D","article-title":"Solution structure of maurotoxin, a scorpion toxin from Scorpio maurus, with high affinity for voltage-gated potassium channels","volume":"29","author":"Blanc","year":"1997","journal-title":"Proteins"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15061","DOI":"10.1021\/bi00254a015","article-title":"Determination of the three-dimensional structure of margatoxin by 1H, 13C, 15N triple-resonance nuclear magnetic resonance spectroscopy","volume":"33","author":"Johnson","year":"1994","journal-title":"Biochemistry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1021\/bi9614390","article-title":"Three-dimensional structure of toxin OSK1 from Orthochirus scrobiculosus scorpion venom","volume":"36","author":"Jaravine","year":"1997","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1016\/S0006-3495(02)75251-X","article-title":"Brownian dynamics simulations of the recognition of the scorpion toxin maurotoxin with the voltage-gated potassium ion channels","volume":"83","author":"Fu","year":"2002","journal-title":"Biophys. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1021\/ci700178w","article-title":"Molecular mechanism of the sea anemone toxin ShK recognizing the Kv1.3 channel explored by docking and molecular dynamic simulations","volume":"47","author":"Jin","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/jmr.1031","article-title":"Molecular mechanism of \u03b4-dendrotoxin-potassium channel recognition explored by docking and molecular dynamic simulations","volume":"24","author":"Jin","year":"2011","journal-title":"J. Mol. Recognit."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e78712","DOI":"10.1371\/journal.pone.0078712","article-title":"A potent and selective peptide blocker of the Kv1.3 channel: Prediction from free-energy simulations and experimental confirmation","volume":"8","author":"Rashid","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4812","DOI":"10.1021\/jp300639x","article-title":"Affinity and selectivity of ShK toxin for the Kv1 potassium channels from free energy simulations","volume":"116","author":"Rashid","year":"2012","journal-title":"J. Phys. Chem. B"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11490","DOI":"10.1021\/jp2061909","article-title":"Charybdotoxin unbinding from the mKv1.3 potassium channel: A combined computational and experimental study","volume":"115","author":"Khabiri","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"ref_66","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_67","doi-asserted-by":"crossref","first-page":"e47253","DOI":"10.1371\/journal.pone.0047253","article-title":"Structural basis of the selective block of Kv1.2 by maurotoxin from computer simulations","volume":"7","author":"Chen","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.3390\/toxins6072149","article-title":"Binding modes of two scorpion toxins to the voltage-gated potassium channel Kv1.3 revealed from molecular dynamics","volume":"6","author":"Chen","year":"2014","journal-title":"Toxins"},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/j.bpj.2013.08.046","article-title":"Molecular dynamics simulations of scorpion toxin recognition by the Ca2+-activated potassium channel KCa3.1","volume":"105","author":"Chen","year":"2013","journal-title":"Biophys. J."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1152\/physrev.00020.2003","article-title":"Conus venoms: A rich source of novel ion channel-targeted peptides","volume":"84","author":"Terlau","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"16989","DOI":"10.1016\/S0021-9258(19)47329-8","article-title":"Active site of \u03bc-conotoxin GIIIA, a peptide blocker of muscle sodium channels","volume":"266","author":"Sato","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8804","DOI":"10.1073\/pnas.83.22.8804","article-title":"Brain voltage-sensitive calcium channel subtypes differentiated by \u03c9-conotoxin fraction GVIA","volume":"83","author":"Reynolds","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0041-0101(03)00099-0","article-title":"A novel conotoxin inhibiting vertebrate voltage-sensitive potassium channels","volume":"42","author":"Kauferstein","year":"2003","journal-title":"Toxicon"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1074\/jbc.273.1.33","article-title":"\u03ba-Conotoxin PVIIA is a peptide inhibiting the Shaker K+ channel","volume":"273","author":"Shon","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.1021\/bi9730341","article-title":"Three-dimensional structure of \u03ba-conotoxin PVIIA, a novel potassium channel-blocking toxin from cone snails","volume":"37","author":"Savarin","year":"1998","journal-title":"Biochemistry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1021\/bi301257p","article-title":"Why the Drosophila Shaker K+ channel is not a good model for ligand binding to voltage-gated Kv1 channels","volume":"59","author":"Mahdavi","year":"2013","journal-title":"Biochemistry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6836","DOI":"10.1021\/ja042641q","article-title":"Electrostatic recognition and induced fit in the \u03ba-PVIIA toxin binding to Shaker potassium channel","volume":"127","author":"Huang","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.toxicon.2006.01.018","article-title":"Venom landscapes: Mining the complexity of spider venoms via a combined cDNA and mass spectrometric approach","volume":"47","author":"Escoubas","year":"2006","journal-title":"Toxicon"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/0896-6273(95)90184-1","article-title":"An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula","volume":"15","author":"Swartz","year":"1995","journal-title":"Neuron"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1046\/j.1432-1327.1999.00726.x","article-title":"Isolation, amino acid sequence and functional assays of SGTx1. The first toxin purified from the venom of the spider scodra griseipes","volume":"265","author":"Marvin","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0026-895X(24)13491-8","article-title":"Heteropodatoxins: Peptides isolated from spider venom that block Kv4.2 potassium channels","volume":"51","author":"Sanguinetti","year":"1997","journal-title":"Mol. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/sj.bjp.0702283","article-title":"Effects of phrixotoxins on the Kv4 family of potassium channels and implications for the role of Ito1 in cardiac electrogenesis","volume":"126","author":"Diochot","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nature01473","article-title":"Functional analysis of an archaebacterial voltage-dependent K+ channel","volume":"422","author":"Ruta","year":"2003","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.toxicon.2006.09.024","article-title":"Tarantula toxins interacting with voltage sensors in potassium channels","volume":"49","author":"Swartz","year":"2007","journal-title":"Toxicon"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/S0041-0101(98)00149-4","article-title":"The cystine knot structure of ion channel toxins and related polypeptides","volume":"36","author":"Norton","year":"1998","journal-title":"Toxicon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1006\/jmbi.2000.3609","article-title":"Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: Common surface features of gating modifier toxins","volume":"297","author":"Takahashi","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1021\/bi0353373","article-title":"Solution structure and functional characterization of SGTx1, a modifier of Kv2.1 channel gating","volume":"43","author":"Lee","year":"2004","journal-title":"Biochemistry"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6015","DOI":"10.1021\/bi0477034","article-title":"Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel","volume":"44","author":"Jung","year":"2005","journal-title":"Biochemistry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e06774","DOI":"10.7554\/eLife.06774","article-title":"Tarantula toxins use common surfaces for interacting with Kv and ASIC ion channels","volume":"4","author":"Gupta","year":"2015","journal-title":"eLife"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1085\/jgp.200309005","article-title":"Molecular surface of tarantula toxins interacting with voltage sensors in KV channels","volume":"123","author":"Wang","year":"2004","journal-title":"J. Gen. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1085\/jgp.200709869","article-title":"Tarantula toxins interact with voltage sensors within lipid membranes","volume":"130","author":"Milescu","year":"2007","journal-title":"J. Gen. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00249-006-0044-z","article-title":"Interaction between K+ channel gate modifier hanatoxin and lipid bilayer membranes analyzed by molecular dynamics simulation","volume":"35","author":"Nishizawa","year":"2006","journal-title":"Eur. Biophys. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"L07","DOI":"10.1529\/biophysj.106.098681","article-title":"SGTx1, a Kv channel gating-modifier toxin, binds to the interfacial region of lipid bilayers","volume":"92","author":"Wee","year":"2007","journal-title":"Biophys. J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"11844","DOI":"10.1021\/bi061111z","article-title":"Vstx1, a modifier of Kv channel gating, localizes to the interfacial region of lipid bilayers","volume":"45","author":"Bemporad","year":"2006","journal-title":"Biochemistry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.bpj.2009.12.4321","article-title":"Interactions between a voltage sensor and a toxin via multiscale simulations","volume":"98","author":"Wee","year":"2010","journal-title":"Biophys. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"E5463","DOI":"10.1073\/pnas.1415324111","article-title":"Structural interactions of a voltage sensor toxin with lipid membranes","volume":"111","author":"Mihailescu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.3390\/toxins4121552","article-title":"Binding of hanatoxin to the voltage sensor of Kv2.1","volume":"4","author":"Chen","year":"2012","journal-title":"Toxins"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/prot.22540","article-title":"Structure prediction for CASP8 with all-atom refinement using Rosetta","volume":"77","author":"Raman","year":"2009","journal-title":"Proteins"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature02743","article-title":"Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers","volume":"430","author":"Suchyna","year":"2004","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00249-008-0386-9","article-title":"Concentration dependent effect of GsMTx4 on mechanosensitive channels of small conductance in E. coli spheroplasts","volume":"38","author":"Hurst","year":"2009","journal-title":"Eur. Biophys. J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1016\/j.bpj.2010.09.022","article-title":"Effects of GsMTx4 on bacterial mechanosensitive channels in inside-out patches from giant spheroplasts","volume":"99","author":"Kamaraju","year":"2010","journal-title":"Biophys. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3390\/toxins5020456","article-title":"Effect of gating modifier toxins on membrane thickness: Implications for toxin effect on gramicidin and mechanosensitive channels","volume":"5","author":"Chen","year":"2013","journal-title":"Toxins"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/0304-4165(93)90082-J","article-title":"A potassium channel toxin from the secretion of the sea anemone Bunodosoma granulifera. Isolation, amino acid sequence and biological activity","volume":"1157","author":"Aneiros","year":"1993","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1074\/jbc.272.7.4302","article-title":"On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures","volume":"272","author":"Dauplais","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1399-3011.1995.tb01068.x","article-title":"Chemical synthesis and characterization of ShK toxin: A potent potassium channel inhibitor from a sea anemone","volume":"46","author":"Pennington","year":"1995","journal-title":"Int. J. Peptide Protein Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"35653","DOI":"10.1074\/jbc.274.50.35653","article-title":"Mapping the functional anatomy of BgK on Kv1.1, Kv1.2, and Kv1.3. Clues to design analogs with enhanced selectivity","volume":"274","author":"Lecoq","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"9124","DOI":"10.1074\/jbc.M109.071266","article-title":"Potassium channel modulation by a toxin domain in matrix metalloprotease 23","volume":"285","author":"Rangaraju","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nsb0496-317","article-title":"Solution structure of ShK toxin, a novel potassium channel inhibitor from a sea anemone","volume":"3","author":"Tudor","year":"1996","journal-title":"Nat. Struct. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"37406","DOI":"10.1074\/jbc.M206205200","article-title":"Structure of the BgK-Kv1.1 complex based on distance restraints identified by double mutant cycles. Molecular basis for convergent evolution of Kv1 channel blockers","volume":"277","author":"Gilquin","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"16407","DOI":"10.1021\/bi962463g","article-title":"An essential binding surface for ShK toxin interaction with rat brain potassium channels","volume":"35","author":"Pennington","year":"1996","journal-title":"Biochemistry"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"16563","DOI":"10.1021\/bi00051a004","article-title":"Determination of the three-dimensional solution structure of noxiustoxin: Analysis of structural differences with related short-chain scorpion toxins","volume":"34","author":"Dauplais","year":"1995","journal-title":"Biochemistry"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.toxicon.2011.07.016","article-title":"Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases","volume":"59","author":"Chi","year":"2012","journal-title":"Toxicon"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1074\/jbc.M706008200","article-title":"The D-diastereomer of ShK toxin selectively blocks voltage-gated K+ channels and inhibits T lymphocyte proliferation","volume":"283","author":"Beeton","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"32697","DOI":"10.1074\/jbc.273.49.32697","article-title":"ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide","volume":"273","author":"Kalman","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"11963","DOI":"10.1021\/bi026400b","article-title":"Mutating a critical lysine in ShK toxin alters its binding configuration in the pore-vestibule region of the voltage-gated potassium channel, Kv1.3","volume":"41","author":"Lanigan","year":"2002","journal-title":"Biochemistry"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e67213","DOI":"10.1371\/journal.pone.0067213","article-title":"Unique mechanism of the interaction between honey bee toxin TPNQ and rKir1.1 potassium channel explored by computational simulations: Insights into the relative insensitivity of channel towards animal toxins","volume":"8","author":"Hu","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.bbamem.2012.09.022","article-title":"Conductance properties of the inwardly rectifying channel, Kir3.2: Molecular and Brownian dynamics study","volume":"1828","author":"Hilder","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1021\/bi301498x","article-title":"Conduction and block of inward rectifier K+ channels: Predicted structure of a potent blocker of Kir2.1","volume":"52","author":"Hilder","year":"2013","journal-title":"Biochemistry"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.csbj.2014.11.004","article-title":"A computational design approach for virtual screening of peptide interactions across K+ channel families","volume":"13","author":"Doupnik","year":"2015","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.bpj.2011.12.041","article-title":"Binding modes of \u03bc-conotoxin to the bacterial sodium channel (NaVAb)","volume":"102","author":"Chen","year":"2012","journal-title":"Biophys. J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1124\/mol.104.008193","article-title":"Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases","volume":"67","author":"Beeton","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1038\/srep04509","article-title":"A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases","volume":"4","author":"Rashid","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"9881","DOI":"10.1038\/srep09881","article-title":"Toxin acidic residue evolutionary function-guided design of de novo peptide drugs for the immunotherapeutic target, the Kv1.3 channel","volume":"5","author":"Chen","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"136a","DOI":"10.1016\/j.bpj.2012.11.778","article-title":"Polymodal, high affinity actions of \u03bc-conotoxins on a bacterial voltage-gated sodium channel","volume":"104","author":"Glavica","year":"2013","journal-title":"Biophys. J."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/12\/4877\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:53:07Z","timestamp":1760215987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/12\/4877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,1]]},"references-count":126,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["toxins7124877"],"URL":"https:\/\/doi.org\/10.3390\/toxins7124877","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,1]]}}}