{"id":1138,"date":"2024-05-26T11:17:36","date_gmt":"2024-05-26T08:17:36","guid":{"rendered":"https:\/\/www.bioeng.ru\/structbiotech\/?page_id=1138"},"modified":"2024-10-23T19:00:02","modified_gmt":"2024-10-23T16:00:02","slug":"channels","status":"publish","type":"page","link":"https:\/\/www.bioeng.ru\/structbiotech\/channels\/","title":{"rendered":"\u0418\u043e\u043d\u043d\u044b\u0435 \u043a\u0430\u043d\u0430\u043b\u044b"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"1138\" class=\"elementor elementor-1138\">\n\t\t\t\t<div class=\"elementor-element elementor-element-5df9d761 e-con-full e-flex e-con e-parent\" data-id=\"5df9d761\" data-element_type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-2d83b56d elementor-invisible elementor-widget elementor-widget-elementskit-heading\" data-id=\"2d83b56d\" data-element_type=\"widget\" data-settings=\"{&quot;_animation&quot;:&quot;fadeIn&quot;}\" 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data-element_type=\"widget\" data-settings=\"{&quot;_animation&quot;:&quot;fadeIn&quot;}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 30-04-2024 *\/\n.elementor-widget-text-editor.elementor-drop-cap-view-stacked .elementor-drop-cap{background-color:#69727d;color:#fff}.elementor-widget-text-editor.elementor-drop-cap-view-framed .elementor-drop-cap{color:#69727d;border:3px solid;background-color:transparent}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap{margin-top:8px}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap-letter{width:1em;height:1em}.elementor-widget-text-editor .elementor-drop-cap{float:left;text-align:center;line-height:1;font-size:50px}.elementor-widget-text-editor .elementor-drop-cap-letter{display:inline-block}<\/style>\t\t\t\t<p>\u0418\u0437\u0443\u0447\u0435\u043d\u0438\u0435 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\u043a\u0430\u043d\u0430\u043b\u043e\u0432 &#8212;\u00a0 \u044d\u043f\u0438\u043b\u0435\u043f\u0441\u0438\u044f, \u0441\u0435\u0440\u0434\u0435\u0447\u043d\u043e-\u0441\u043e\u0441\u0443\u0434\u0438\u0441\u0442\u044b\u0435 \u0431\u043e\u043b\u0435\u0437\u043d\u0438 \u0438 \u043d\u0435\u0439\u0440\u043e\u0434\u0435\u0433\u0435\u043d\u0435\u0440\u0430\u0442\u0438\u0432\u043d\u044b\u0435 \u0440\u0430\u0441\u0441\u0442\u0440\u043e\u0439\u0441\u0442\u0432\u0430.<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-3c97bab1 e-con-full e-flex e-con e-parent\" data-id=\"3c97bab1\" data-element_type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-19fda3a7 elementor-invisible elementor-widget elementor-widget-elementskit-heading\" data-id=\"19fda3a7\" data-element_type=\"widget\" data-settings=\"{&quot;_animation&quot;:&quot;fadeIn&quot;}\" data-widget_type=\"elementskit-heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<div class=\"ekit-wid-con\" ><div class=\"ekit-heading elementskit-section-title-wraper text_left   ekit_heading_tablet-   ekit_heading_mobile-\"><h1 class=\"ekit-heading--title elementskit-section-title \">\u041f\u0443\u0431\u043b\u0438\u043a\u0430\u0446\u0438\u0438 \u0433\u0440\u0443\u043f\u043f\u044b \u043f\u043e \u043d\u0430\u043f\u0440\u0430\u0432\u043b\u0435\u043d\u0438\u044e<\/h1><\/div><\/div>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-687efeaa e-con-full e-flex e-con e-parent\" data-id=\"687efeaa\" data-element_type=\"container\">\n\t\t<div class=\"elementor-element elementor-element-191b5fcf e-con-full e-flex e-con e-child\" data-id=\"191b5fcf\" data-element_type=\"container\" data-settings=\"{&quot;animation&quot;:&quot;none&quot;,&quot;animation_tablet&quot;:&quot;none&quot;}\">\n\t\t\t\t<div class=\"elementor-element elementor-element-ff45576 elementor-widget__width-inherit elementor-widget elementor-widget-elementskit-heading\" data-id=\"ff45576\" data-element_type=\"widget\" data-widget_type=\"elementskit-heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<div class=\"ekit-wid-con\" ><div class=\"ekit-heading elementskit-section-title-wraper text_left   ekit_heading_tablet-   ekit_heading_mobile-\"><a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jpcb.4c03182\"><h3 class=\"ekit-heading--title elementskit-section-title \">A Deep Learning Approach to Uncover Voltage-Gated Ion Channels\u2019 Intermediate States<\/h3><\/a><h6 class=\"ekit-heading--subtitle elementskit-section-subtitle  \">\n\t\t\t\t\t\tJulia Kacher, Olga S. Sokolova, and Mounir Tarek\n\t\t\t\t\t<\/h6><\/div><\/div>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-40eb1a8a e-con-full e-flex e-con e-child\" data-id=\"40eb1a8a\" data-element_type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-6639f218 elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"6639f218\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p>Owing to recent advancements in cryo-electron microscopy, voltage-gated ion channels have gained a greater comprehension of their structural characteristics. However, a significant enigma remains unsolved for a large majority of these channels: their gating mechanism. This mechanism, which encompasses the conformational changes between open and closed states, is pivotal to their proper functioning. Beyond the binary states of open and closed, an ensemble of intermediate states defines the transition path in-between. Due to the lack of experimental data, one might resort to molecular dynamics simulations as an alternative to decipher these states and the transitions between them. However, the high-energy barriers and the colossal time scales involved hinder access to the latter. We present here an application of deep learning as a reliable pipeline for a comprehensive exploration of voltage-gated ion channel conformational rearrangements during gating. We showcase the pipeline performance specifically on the Kv1.2 voltage sensor domain and confront the results with existing data. We demonstrate how our physics-based deep learning approach contributes to the theoretical understanding of these channels and how it might provide further insights into the exploration of channelopathies. <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jpcb.4c03182\">DOI<\/a>\u00a0<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-47109f21 e-con-full e-flex e-con e-child\" data-id=\"47109f21\" data-element_type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-5857b6d2 elementor-widget elementor-widget-image\" data-id=\"5857b6d2\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 30-04-2024 *\/\n.elementor-widget-image{text-align:center}.elementor-widget-image a{display:inline-block}.elementor-widget-image a img[src$=\".svg\"]{width:48px}.elementor-widget-image img{vertical-align:middle;display:inline-block}<\/style>\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"500\" height=\"299\" src=\"https:\/\/www.bioeng.ru\/structbiotech\/wp-content\/uploads\/sites\/3\/2024\/10\/deep_learning.gif\" class=\"attachment-large size-large wp-image-2996\" alt=\"\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-fab1495 e-con-full e-flex e-con e-child\" data-id=\"fab1495\" data-element_type=\"container\" data-settings=\"{&quot;animation&quot;:&quot;none&quot;,&quot;animation_tablet&quot;:&quot;none&quot;}\">\n\t\t\t\t<div class=\"elementor-element elementor-element-a1d3b7a elementor-widget__width-inherit elementor-widget elementor-widget-elementskit-heading\" data-id=\"a1d3b7a\" data-element_type=\"widget\" data-widget_type=\"elementskit-heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<div class=\"ekit-wid-con\" ><div class=\"ekit-heading elementskit-section-title-wraper text_left   ekit_heading_tablet-   ekit_heading_mobile-\"><a href=\"https:\/\/doi.org\/10.3390\/genes13040559\"><h3 class=\"ekit-heading--title elementskit-section-title \">Variable Clinical Appearance of the Kir2.1 Rare Variants in Russian Patients with Long QT Syndrome<\/h3><\/a><h6 class=\"ekit-heading--subtitle elementskit-section-subtitle  \">\n\t\t\t\t\t\tElena Zaklyazminskaya, Margarita Polyak, Anna Shestak, Mariam Sadekova, Vera Komoliatova, Irina Kiseleva, Leonid Makarov, Dmitriy Podolyak, Grigory Glukhov, Han Zhang, Denis Abramochkin, Olga S Sokolova\n\t\t\t\t\t<\/h6><\/div><\/div>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-7b4314e e-con-full e-flex e-con e-child\" data-id=\"7b4314e\" data-element_type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-67227908 elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"67227908\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div id=\"eng-abstract\" class=\"abstract-content selected\"><p><strong class=\"sub-title\"> Background: <\/strong> The <i>KCNJ2<\/i> gene encodes inward rectifier Kir2.1 channels, maintaining resting potential and cell excitability. Presumably, clinical phenotypes of mutation carriers correlate with ion permeability defects. Loss-of-function mutations lead to QTc prolongation with variable dysmorphic features, whereas gain-of-function mutations cause short QT syndrome and\/or atrial fibrillation.<\/p><p><strong class=\"sub-title\"> Methods: <\/strong> We screened 210 probands with Long QT syndrome for mutations in the <i>KCNJ2<\/i> gene. The electrophysiological study was performed for the p.Val93Ile variant in the transfected CHO-K1 cells.<\/p><p><strong class=\"sub-title\"> Results: <\/strong> We found three rare genetic variants, p.Arg67Trp, p.Val93Ile, and p.R218Q, in three unrelated LQTS probands. Probands with p.Arg67Trp and p.R218Q had a phenotype typical for Andersen-Tawil (ATS), and the p.Val93Ile carrier had lone QTc prolongation. Variant p.Val93Ile was initially described as a gain-of-function pathogenic mutation causing familial atrial fibrillation. We validated electrophysiological features of this variant in CHO-K1 cells, but no family members of these patients had atrial fibrillation. Using ACMG (2015) criteria, we re-assessed this variant as a variant of unknown significance (class III).<\/p><p><strong class=\"sub-title\"> Conclusions: <\/strong> LQT7 is a rare form of LQTS in Russia, and accounts for 1% of the LQTS cohort. Variant p.Val93Ile leads to a gain-of-function effect in the different cell lines, but its clinical appearance is not so consistent. The clinical significance of this variant might be overestimated. <a href=\"https:\/\/doi.org\/10.3390\/genes13040559\">DOI<\/a><\/p><\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-149478a9 e-flex e-con-boxed e-con e-child\" data-id=\"149478a9\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-5e86a6cc elementor-widget elementor-widget-image\" data-id=\"5e86a6cc\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" width=\"765\" height=\"260\" src=\"https:\/\/www.bioeng.ru\/structbiotech\/wp-content\/uploads\/sites\/3\/2024\/10\/genes-13-00559-g005.jpg\" class=\"attachment-large size-large wp-image-3002\" alt=\"\" srcset=\"https:\/\/www.bioeng.ru\/structbiotech\/wp-content\/uploads\/sites\/3\/2024\/10\/genes-13-00559-g005.jpg 765w, https:\/\/www.bioeng.ru\/structbiotech\/wp-content\/uploads\/sites\/3\/2024\/10\/genes-13-00559-g005-300x102.jpg 300w, https:\/\/www.bioeng.ru\/structbiotech\/wp-content\/uploads\/sites\/3\/2024\/10\/genes-13-00559-g005-18x6.jpg 18w\" sizes=\"(max-width: 765px) 100vw, 765px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-cdecc51 e-con-full e-flex e-con e-child\" data-id=\"cdecc51\" data-element_type=\"container\" data-settings=\"{&quot;animation&quot;:&quot;none&quot;,&quot;animation_tablet&quot;:&quot;none&quot;}\">\n\t\t\t\t<div class=\"elementor-element elementor-element-184b626 elementor-widget__width-inherit elementor-widget elementor-widget-elementskit-heading\" data-id=\"184b626\" data-element_type=\"widget\" data-widget_type=\"elementskit-heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<div class=\"ekit-wid-con\" ><div class=\"ekit-heading elementskit-section-title-wraper text_left   ekit_heading_tablet-   ekit_heading_mobile-\"><a href=\"http:\/\/doi.org\/10.1007\/978-1-0716-3818-7_4\"><h3 class=\"ekit-heading--title elementskit-section-title \">Purification of Potassium Ion Channels Using Styrene\u2013Maleic Acid Copolymers<\/h3><\/a><h6 class=\"ekit-heading--subtitle elementskit-section-subtitle  \">\n\t\t\t\t\t\tGlukhov Grigory, Karlova Maria, Kravchuk Ekaterina, Glukhova Anna, Trifonova Elizaveta, Sokolova Olga S.\n\t\t\t\t\t<\/h6><\/div><\/div>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-9fabf25 e-con-full e-flex e-con e-child\" data-id=\"9fabf25\" data-element_type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-51ccb47 elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"51ccb47\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p>Structural studies require the production of target proteins in large quantities and with a high degree of purity. For membrane proteins, the bottleneck in determining their structure is the extraction of the target protein from the cell membranes. A detergent that improperly mimics the hydrophobic environment of the protein of interest can also significantly alter its structure. Recently, using lipodiscs with styrene\u2013maleic acid (SMA), copolymers became a promising strategy for the purification of membrane proteins. Here, we describe in detail the one-step affinity purification of potassium ion channels solubilized in SMA and sample preparation for future structural studies. <a href=\"http:\/\/doi.org\/10.1007\/978-1-0716-3818-7_4\">DOI<\/a>\u00a0<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-eb92e13 e-con-full e-flex e-con e-child\" data-id=\"eb92e13\" data-element_type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-c50b0e3 elementor-widget elementor-widget-image\" data-id=\"c50b0e3\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" width=\"685\" height=\"360\" src=\"https:\/\/www.bioeng.ru\/structbiotech\/wp-content\/uploads\/sites\/3\/2024\/10\/540109_1_en_4_fig3_html.png\" class=\"attachment-large size-large wp-image-2998\" alt=\"\" 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class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/www.bioeng.ru\/structbiotech\/articles\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">\u0412\u0441\u0435 \u043f\u0443\u0431\u043b\u0438\u043a\u0430\u0446\u0438\u0438 \u0433\u0440\u0443\u043f\u043f\u044b<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>\u0418\u043e\u043d\u043d\u044b\u0435 \u043a\u0430\u043d\u0430\u043b\u044b \u0418\u0437\u0443\u0447\u0435\u043d\u0438\u0435 \u0441\u0442\u0440\u0443\u043a\u0442\u0443\u0440 \u0438\u043e\u043d\u043d\u044b\u0445 \u043a\u0430\u043d\u0430\u043b\u043e\u0432 \u0438\u043c\u0435\u0435\u0442 \u043a\u043b\u044e\u0447\u0435\u0432\u043e\u0435 \u0437\u043d\u0430\u0447\u0435\u043d\u0438\u0435 \u0434\u043b\u044f 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[&hellip;]<\/p>\n","protected":false},"author":10,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"elementor_header_footer","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","ast-site-content-layout":"full-width-container","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"disabled","ast-breadcrumbs-content":"","ast-featured-img":"disabled","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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