{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:10:12Z","timestamp":1778055012693,"version":"3.51.4"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2012,2,6]],"date-time":"2012-02-06T00:00:00Z","timestamp":1328486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>During the development of selective peptides against highly homologous targets, a reliable tool is sought that can predict information on both mechanisms of binding and relative affinities. These tools must first be tested on known profiles before application on novel therapeutic candidates. We therefore present a comparative docking protocol in HADDOCK using critical motifs, and use it to \u201cpredict\u201d the various selectivity profiles of several major \u03b1KTX scorpion toxin families versus Kv1.1, Kv1.2 and Kv1.3. By correlating results across toxins of similar profiles, a comprehensive set of functional residues can be identified. Reasonable models of channel-toxin interactions can be then drawn that are consistent with known affinity and mutagenesis. Without biological information on the interaction, HADDOCK reproduces mechanisms underlying the universal binding of \u03b1KTX-2 toxins, and Kv1.3 selectivity of \u03b1KTX-3 toxins. The addition of constraints encouraging the critical lysine insertion confirms these findings, and gives analogous explanations for other families, including models of partial pore-block in \u03b1KTX-6. While qualitatively informative, the HADDOCK scoring function is not yet sufficient for accurate affinity-ranking. False minima in low-affinity complexes often resemble true binding in high-affinity complexes, despite steric\/conformational penalties apparent from visual inspection. This contamination significantly complicates energetic analysis, although it is usually possible to obtain correct ranking via careful interpretation of binding-well characteristics and elimination of false positives. Aside from adaptations to the broader potassium channel family, we suggest that this strategy of comparative docking can be extended to other channels of interest with known structure, especially in cases where a critical motif exists to improve docking effectiveness.<\/jats:p>","DOI":"10.3390\/toxins4020110","type":"journal-article","created":{"date-parts":[[2012,2,6]],"date-time":"2012-02-06T11:20:07Z","timestamp":1328527207000},"page":"110-138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Developing a Comparative Docking Protocol for the Prediction of Peptide Selectivity Profiles: Investigation of Potassium Channel Toxins"],"prefix":"10.3390","volume":"4","author":[{"given":"Po-Chia","family":"Chen","sequence":"first","affiliation":[{"name":"School of Physics, Building A28, University of Sydney, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serdar","family":"Kuyucak","sequence":"additional","affiliation":[{"name":"School of Physics, Building A28, University of Sydney, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.2174\/138161208785777441","article-title":"Animal toxins acting on voltage-gated potassium channels.","volume":"14","author":"Mouhat","year":"2008","journal-title":"Curr. Pharmaceut. Des."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.2174\/0929867043363947","article-title":"Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple sclerosis and other autoimmune diseases.","volume":"11","author":"Norton","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.pharmthera.2005.10.006","article-title":"Potassium channel blockers in multiple sclerosis: Neuronal K-V channels and effects of symptomatic treatment.","volume":"111","author":"Judge","year":"2006","journal-title":"Pharmacol. Therapeut."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1111\/j.1476-5381.2009.00362.x","article-title":"The K+ channels K(Ca)3.1 and K(v)1.3 as novel targets for asthma therapy","volume":"157","author":"Bradding","year":"2009","journal-title":"Brit. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13373","DOI":"10.1073\/pnas.231376298","article-title":"Distinct potassium channels on pain-sensing neurons.","volume":"98","author":"Rasband","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Takeda, M., Tsuboi, Y., Kitagawa, J., Nakagawa, K., Iwata, K., and Matsumoto, S. (2011). Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain.. Mol. Pain, 7.","DOI":"10.1186\/1744-8069-7-5"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0041-0101(00)00162-8","article-title":"Twenty years of dendrotoxins.","volume":"39","author":"Harvey","year":"2001","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.toxicon.2006.09.015","article-title":"The interaction of spider gating modifier peptides with voltage-gated potassium channels.","volume":"49","author":"Huang","year":"2007","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.toxicon.2004.03.022","article-title":"Current views on scorpion toxins specific for K+-channels.","volume":"43","author":"Possani","year":"2004","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/0041-0101(95)00013-C","article-title":"Characterization of a potassium channel toxin from the Caribbean sea-anemone Stichodactyla-helianthus.","volume":"33","author":"Castaneda","year":"1995","journal-title":"Toxicon"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0165-6147(99)01398-X","article-title":"A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies.","volume":"20","author":"Tytgat","year":"1999","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1124\/mol.63.2.409","article-title":"Maurotoxin: A potent inhibitor of intermediate conductance Ca2+\u2013activated potassium channels.","volume":"63","author":"Castle","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/prot.10341","article-title":"Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: Selectivity between voltage-gated and Maxi-K channels.","volume":"52","author":"Gao","year":"2003","journal-title":"Proteins Struct. Func. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.1021\/bi700150t","article-title":"Revealing the molecular determinants of neurotoxin specificity for calcium-activated versus voltage-dependent potassium channels.","volume":"46","author":"Giangiacomo","year":"2007","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1074\/jbc.275.2.1201","article-title":"Structure-guided transformation of charybdotoxin yields an analog that selectively targets Ca2+-activated over voltage-gated K+ channels.","volume":"275","author":"Rauer","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_18","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_19","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_20","doi-asserted-by":"crossref","first-page":"31095","DOI":"10.1074\/jbc.M304271200","article-title":"A maurotoxin with constrained standard disulfide bridging\u2014Innovative strategy of chemical synthesis, pharmacology, and docking on K+ channels.","volume":"278","author":"Andreotti","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1042\/bj20030977","article-title":"Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels.","volume":"377","author":"Jouirou","year":"2004","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/jcc.21276","article-title":"Protein-Protein Docking Dealing With the Unknown.","volume":"31","author":"Moreira","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jcc.540150503","article-title":"ICM\u2014A new method for protein modelling and design\u2014applications to docking and structure prediction from the distorted native conformations.","volume":"15","author":"Abagyan","year":"1994","journal-title":"J. Comput. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"HADDOCK: A protein-protein docking approach based on biochemical or biophysical information.","volume":"125","author":"Dominguez","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/prot.21373","article-title":"ZRANK: Reranking protein docking predictions with an optimized energy function.","volume":"67","author":"Pierce","year":"2007","journal-title":"Proteins Struct. Func. Bioinf."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.str.2007.06.007","article-title":"The Third CAPRI Assessment Meeting\u2014Toronto, Canada, April 20\u201321, 2007","volume":"15","author":"Janin","year":"2007","journal-title":"Structure"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.jmb.2008.05.042","article-title":"Conformer selection and induced fit in flexible backbone protein-protein docking using computational and NMR ensembles.","volume":"381","author":"Chaudhury","year":"2008","journal-title":"J Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5144","DOI":"10.1021\/jp911085d","article-title":"Dynamic Ligand-Induced-Fit Simulation via Enhanced Conformational Samplings and Ensemble Dockings: A Survivin Example.","volume":"114","author":"Park","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.sbi.2006.02.002","article-title":"Flexible protein-protein docking.","volume":"16","author":"Bonvin","year":"2006","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/prot.22170","article-title":"Principles of flexible protein-protein docking.","volume":"73","author":"Andrusier","year":"2008","journal-title":"Proteins Struct. Func. Bioinf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.str.2009.02.010","article-title":"Binding of Small-Molecule Ligands to Proteins: \u201dWhat You See\u201d Is Not Always What You Get","volume":"17","author":"Mobley","year":"2009","journal-title":"Structure"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1021\/ct8002354","article-title":"Standard Free Energy of Binding from a One-Dimensional Potential of Mean Force.","volume":"5","author":"Doudou","year":"2009","journal-title":"J. Chem. Theory Comput."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1023\/A:1016357811882","article-title":"Further development and validation of empirical scoring functions for structure-based binding affinity prediction","volume":"16","author":"Wang","year":"2002","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/prot.21082","article-title":"Protein-ligand docking: Current status and future challenges.","volume":"65","author":"Sousa","year":"2006","journal-title":"Proteins Struct. Func. Bioinf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/med.20067","article-title":"Combining docking and molecular dynamic simulations in drug design.","volume":"26","author":"Alonso","year":"2006","journal-title":"Med. Res. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/prot.21723","article-title":"HADDOCK versus HADDOCK: New features and performance of HADDOCK2.0 on the CAPRI targets.","volume":"69","author":"Krzeminski","year":"2007","journal-title":"Proteins Struct. Func. Bioinf."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD.","volume":"26","author":"Phillips","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.toxicon.2005.06.001","article-title":"Novel alpha-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1K(+) channels of T cells","volume":"46","author":"Somodi","year":"2005","journal-title":"Toxicon"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13473","DOI":"10.1021\/bi971044w","article-title":"Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels.","volume":"36","author":"RomiLebrun","year":"1997","journal-title":"Biochemistry"},{"key":"ref_43","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_44","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_45","doi-asserted-by":"crossref","first-page":"10094","DOI":"10.1073\/pnas.89.21.10094","article-title":"Selective blockers of voltage-gated K+ channels depolarize human lymphocyte-T\u2014mechanism of the antiproliferative effect of charybdotoxin.","volume":"89","author":"Leonard","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1074\/jbc.273.5.2639","article-title":"Subunit composition of brain voltage-gated potassium channels determined by hongotoxin-1, a novel peptide derived from Centruroides limbatus venom","volume":"273","author":"Koschak","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6834","DOI":"10.1021\/bi00188a012","article-title":"Purification and characterization of 3 inhibitors of voltage-dependent K+ channels from Leiurus-quinquestriatus var hebraeus venom.","volume":"33","author":"Garcia","year":"1994","journal-title":"Biochemistry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1110\/ps.073122908","article-title":"Chemical synthesis and H-1-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":"Prot. Sci."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0022-3565(24)37521-4","article-title":"Toxin and subunit specificity of blocking affinity of three peptide toxins for heteromultimeric, voltage-gated potassium channels expressed in Xenopus oocytes","volume":"285","author":"Hopkins","year":"1998","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/sj.bjp.0705343","article-title":"Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel Kv1.3","volume":"139","author":"Rodrigues","year":"2003","journal-title":"Brit. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.1046\/j.1432-1327.2000.01577.x","article-title":"Chemical synthesis and characterization of Pi1, a scorpion toxin from Pandinus imperator active on K+ channels","volume":"267","author":"Fajloun","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"55690","DOI":"10.1074\/jbc.M410055200","article-title":"Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins.","volume":"279","author":"Regaya","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13605","DOI":"10.1074\/jbc.275.18.13605","article-title":"Synthesis, H-1 NMR structure, and activity of a three-disulfide-bridged maurotoxin analog designed to restore the consensus motif of scorpion toxins.","volume":"275","author":"Fajloun","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0014-5793(97)00285-8","article-title":"Maurotoxin, a four disulfide bridge toxin from Scorpio maurus venom: Purification, structure and action on potassium channels.","volume":"406","author":"Kharrat","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/prot.20509","article-title":"Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments ligand affinity.","volume":"60","author":"Chagot","year":"2005","journal-title":"Proteins Struct. Func. Bioinf."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1002\/prot.20681","article-title":"The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily.","volume":"61","author":"Carrega","year":"2005","journal-title":"Proteins Struct. Func. Bioinf."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1046\/j.1432-1033.2003.03743.x","article-title":"Synthesis and characterization of Pi4, a scorpion toxin from Pandinus imperator that acts on K+ channels","volume":"270","author":"Mosbah","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S0026-895X(25)09545-8","article-title":"Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels.","volume":"50","author":"Rogowski","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1006\/bbrc.1997.8018","article-title":"Pandinus imperator scorpion venom blocks voltage-gated K+ channels in human lymphocytes.","volume":"242","author":"Peter","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","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_63","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/psc.630","article-title":"Contribution of the functional dyad of animal toxins acting on voltage-gated Kv1-type channels.","volume":"11","author":"Mouhat","year":"2005","journal-title":"J. Pept. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"15834","DOI":"10.1021\/bi051656d","article-title":"Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex.","volume":"44","author":"Yu","year":"2005","journal-title":"Biochemistry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/prot.22102","article-title":"Very fast prediction and rationalization of pKa values for protein-ligand complexes.","volume":"73","author":"Bas","year":"2008","journal-title":"Proteins Struct. Func. Bioinf."},{"key":"ref_66","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_67","doi-asserted-by":"crossref","first-page":"31013","DOI":"10.1074\/jbc.271.49.31013","article-title":"The signature sequence of voltage-gated potassium channels projects into the external vestibule.","volume":"271","author":"Aiyar","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1124\/mol.104.002774","article-title":"Mapping of maurotoxin binding sites on hKv1.2, hKv1.3, and hIKCa1 channels","volume":"66","author":"Visan","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1021\/pr9009854","article-title":"Are Scoring Functions in Protein-Protein Docking Ready To Predict Interactomes? Clues from a Novel Binding Affinity Benchmark","volume":"9","author":"Kastritis","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1016\/j.bpj.2008.12.3952","article-title":"Mechanism and Energetics of Charybdotoxin Unbinding from a Potassium Channel from Molecular Dynamics Simulations.","volume":"96","author":"Chen","year":"2009","journal-title":"Biophys. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1016\/j.bpj.2011.03.052","article-title":"Accurate Determination of the Binding Free Energy for KcsA-Charybdotoxin Complex from the Potential of Mean Force Calculations with Restraints.","volume":"100","author":"Chen","year":"2011","journal-title":"Biophys. J."},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1016\/j.toxicon.2008.03.027","article-title":"OdK2, a Kv1.3 channel-selective toxin from the venom of the Iranian scorpion Odonthobuthus doriae","volume":"51","author":"Vandendriessche","year":"2008","journal-title":"Toxicon"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature10238","article-title":"The crystal structure of a voltage-gated sodium channel.","volume":"475","author":"Payandeh","year":"2011","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.2174\/138161208785777423","article-title":"Animal peptides targeting voltage-activated sodium channels.","volume":"14","author":"Billen","year":"2008","journal-title":"Curr. Pharmaceut. Des."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0006-3495(03)74654-2","article-title":"Novel interactions identified between mu-conotoxin and the Na(+) channel domain IP-loop: Implications for toxin-pore binding geometry.","volume":"85","author":"Xue","year":"2003","journal-title":"Biophys. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.pharmthera.2010.08.006","article-title":"Acid-Sensing Ion Channels (ASICs): Pharmacology and implication in pain.","volume":"128","author":"Deval","year":"2010","journal-title":"Pharmacol. 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