{"id":6856,"date":"2020-09-20T17:26:53","date_gmt":"2020-09-20T14:26:53","guid":{"rendered":"https:\/\/www.ortaakarsu.net\/?p=6856"},"modified":"2020-10-24T21:57:35","modified_gmt":"2020-10-24T18:57:35","slug":"yanastirma-protein-ligand-yanastirma","status":"publish","type":"post","link":"https:\/\/www.ortaakarsu.net\/?p=6856","title":{"rendered":"Yana\u015ft\u0131rma Nedir? Molek\u00fcler Docking Nas\u0131l Yap\u0131l\u0131r?"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Yana\u015ft\u0131rma, yani molek\u00fcler docking (veya molek\u00fcler kenetlenme) pek \u00e7ok ad\u0131mdan olu\u015fan karma\u015f\u0131k bir s\u00fcre\u00e7tir. Bu ad\u0131mlar\u0131 bir \u00f6rnekle ele alaca\u011f\u0131z. Bunun i\u00e7in de yap\u0131lan ba\u015fka bir \u00e7al\u0131\u015fmadan yola \u00e7\u0131kaca\u011f\u0131z.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Protein-ligand etkile\u015fimine \u00f6rnek olarak alttaki videoyu izleyebilirsiniz. Bu videoda Covid-19 polimeraz enzimi ile remdesivir molek\u00fcl\u00fcn\u00fcn birbirine kenetli hali g\u00f6r\u00fcnmekte. <\/p>\n\n\n\n<figure class=\"wp-block-embed-youtube wp-block-embed is-type-video is-provider-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<div class=\"video-shortcode\"><iframe title=\"Remdesivir ve Covid-19 RNA polimeraz kompleksi.\" width=\"1200\" height=\"675\" src=\"https:\/\/www.youtube.com\/embed\/CuPMc1zQD38?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe><\/div>\n<\/div><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Bu uygulamada Shr\u00f6dinger Yaz\u0131l\u0131m firmas\u0131n\u0131n Maestro aray\u00fcz\u00fc ve g\u00f6m\u00fcl\u00fc yaz\u0131l\u0131mlar yana\u015ft\u0131rma i\u015flemi  kullan\u0131lm\u0131\u015ft\u0131r. Kenetlenme hesaplamalar\u0131 i\u00e7in &nbsp;Glutatyon Reduktaz(GR) enzimi i\u00e7in <a href=\"https:\/\/www.rcsb.org\/structure\/1GRA\">PDB kodu 1GRA<\/a> olan X-\u0131\u015f\u0131n\u0131 k\u0131r\u0131n\u0131m\u0131 methoduyla, yap\u0131s\u0131 2 \u00c5&nbsp;\u00e7\u00f6z\u00fcn\u00fcrl\u00fckle belirlenen kristal verisi kullan\u0131ld\u0131.&nbsp;Kenetleme i\u015flemi i\u00e7in Maestro 11.1\u2019in Glide molek\u00fcler docking(kenetleme) paketi&nbsp;kullan\u0131lm\u0131\u015ft\u0131r. Bu protein yap\u0131s\u0131 ile ilgili daha \u00e7ok bilgi i\u00e7in: <strong>DOI:&nbsp;<\/strong><a href=\"http:\/\/doi.org\/10.2210\/pdb1GRA\/pdb\" target=\"_blank\" rel=\"noreferrer noopener\">10.2210\/pdb1GRA\/pdb<\/a> adresini ziyaret edebilirsiniz. Protein-ligand yana\u015ft\u0131rma i\u015flemi i\u00e7in yap\u0131lmas\u0131 gereken belli ba\u015fl\u0131 i\u015flemler i\u00e7in ad\u0131m ad\u0131m inceleme yap\u0131lacakt\u0131r.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"586\" height=\"299\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-42.png\" alt=\"Yana\u015ft\u0131rma i\u015flemi i\u00e7in kullan\u0131lan GR enzimin g\u00f6rn\u00fct\u00fcs\u00fc\" class=\"wp-image-6860\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-42-300x153.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-42-500x255.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-42-550x281.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-42.png 586w\" sizes=\"(max-width: 586px) 100vw, 586px\" \/><figcaption>Glutatyon Red\u00fcktaz g\u00f6r\u00fcnt\u00fcs\u00fc<\/figcaption><\/figure><\/div>\n\n\n\n<p class=\"wp-block-paragraph\">Glutatyon red\u00fcktaz enzimi GSSG yi(yani oksitlenmi\u015f glutatyonu) glutatyona \u00e7eviren enzimdir. Bu enzim ile ilgili daha \u00e7ok bilgi almak i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=95\">Glutatyon Red\u00fcktaz Enzim Aktivitesi<\/a> adl\u0131 yaz\u0131y\u0131 okuyabilirsiniz.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"500\" height=\"168\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/glutatyonreduktaz_mekanizma.gif\" alt=\"\" class=\"wp-image-97\"\/><figcaption>glutatyon red\u00fcktaz enziminin i\u015flevi<\/figcaption><\/figure><\/div>\n\n\n\n<h2 class=\"wp-block-heading\">Yana\u015ft\u0131rma \u0130\u015flemi ve Protein-Ligand Etkile\u015fimleri<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Yana\u015ft\u0131rma i\u015flemi i\u00e7in toplamda be\u015f ligand kullan\u0131lm\u0131\u015ft\u0131r. Molek\u00fcler yana\u015ft\u0131rma i\u015flemine ge\u00e7ilmeden \u00f6nce ligandlar molek\u00fcler docking i\u00e7in uygun hale getirilmelidir. Bunun i\u00e7in \u00f6ncelikle be\u015f ligand\u0131n her birinin en d\u00fc\u015f\u00fck enerjili be\u015f konformasyonu Maestro\u2019in Jaguar paket program\u0131 kullan\u0131larak \u00fcretildi. Burada ama\u00e7 farkl\u0131 konformasyonlarda iyi ba\u011flanan ligandlar\u0131n hesaplamada \u0131skalanmas\u0131n\u0131n \u00f6n\u00fcne ge\u00e7ilmesidir. Bu konformasyonlar\u0131n her biri Maestro 11.1\u2019in&nbsp;LigPrep program\u0131n Epik g\u00f6m\u00fcl\u00fc yaz\u0131l\u0131m\u0131 kullan\u0131larak OPLS_2005 kuvvet alan\u0131nda pH 7.4\u2019de kenetlenme i\u015flemine uygun hale getirildi.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Protein yap\u0131n\u0131n protein-ligand yana\u015ft\u0131rma i\u015flemine uygun hale getirilmesi i\u00e7in protein yan\u0131n bu i\u015fleme haz\u0131r hale getirilmesi gerekmektedir.  Bunun i\u00e7in Maestro\u2019nun \u201cProtein Haz\u0131rlama Sihirbaz\u0131\u201d kullan\u0131ld\u0131. Protein verisi indirildikten sonra zincirinde eksik amino asitlerin olup olmad\u0131\u011f\u0131 kontrol edildi ve her hangi bir sorun olmad\u0131\u011f\u0131 g\u00f6r\u00fcld\u00fc. Yana\u015ft\u0131rma i\u015flemi i\u00e7in  Preprocess i\u015flemi sadece pH de\u011fi\u015ftirilerek yap\u0131ld\u0131 di\u011fer se\u00e7enekler fabrika ayarlar\u0131nda tutuldu. Ligandlar\u0131n 3 \u00c5&nbsp;uza\u011f\u0131ndaki su molek\u00fclleri silindi.&nbsp;&nbsp;Hidrojen ba\u011flar\u0131 7.4 pH i\u00e7in modifiye edildikten sonra OPLS_2005 kuvvet alan\u0131nda minimizasyon i\u015flemi yap\u0131ld\u0131.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Yana\u015ft\u0131rma i\u015fleminde ligand\u0131n ba\u011flanaca\u011f\u0131 b\u00f6lgenin yaz\u0131l\u0131ma g\u00f6sterilmesi i\u00e7in kafes haz\u0131rlama i\u015flemi uygulan\u0131r. GR\u2019nin aktif merkezinde bulunan GSSG molek\u00fcl\u00fc i\u00e7in yap\u0131ld\u0131. Bu i\u015flem i\u00e7in \u201cResept\u00f6r Kafes Haz\u0131rlama\u201d kullan\u0131ld\u0131. Kafes boyutlar\u0131 GSSG\u2019nin boyutlar\u0131na g\u00f6re i\u00e7 \u00e7er\u00e7evelendi ve d\u0131\u015f \u00e7er\u00e7eve fabrika ayarlar\u0131nda tutuldu. Di\u011fer se\u00e7enekler fabrika ayarlarlar\u0131nda tutuldu.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Protein-Ligand Yan\u015ft\u0131rma \u0130\u015fleminin Sonucu<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Kenetleme i\u015flemi i\u00e7in \u201c<strong>Ligand Docking<\/strong>\u201d kullan\u0131ld\u0131. Kenetleme i\u015fleminin hassasiyet ayar\u0131 XP olarak ayarland\u0131 ve kenetlenme i\u015fleminde denenen her ligand i\u00e7in be\u015f poz istendi ve kenetleme i\u015flemi ba\u015flat\u0131ld\u0131.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"586\" height=\"310\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-40.png\" alt=\"Yana\u015ft\u0131rma i\u015fleminin sonu\u00e7 g\u00f6r\u00fcnt\u00fcs\u00fc\" class=\"wp-image-6858\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-40-300x159.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-40-500x265.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-40-550x291.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-40.png 586w\" sizes=\"(max-width: 586px) 100vw, 586px\" \/><figcaption>Yana\u015ft\u0131rma i\u015fleminin 3D sonu\u00e7 g\u00f6r\u00fcnt\u00fcs\u00fc.<\/figcaption><\/figure><\/div>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"586\" height=\"535\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-41.png\" alt=\"\" class=\"wp-image-6859\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-41-300x274.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-41-500x456.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-41-550x502.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-41.png 586w\" sizes=\"(max-width: 586px) 100vw, 586px\" \/><figcaption>Ligand yana\u015ft\u0131rma i\u015fleminin 2D g\u00f6r\u00fcnt\u00fcs\u00fc.<\/figcaption><\/figure><\/div>\n\n\n\n<p class=\"wp-block-paragraph\">Molek\u00fcler docking veya bir di\u011fer ad\u0131yla protein-ligand <strong>yana\u015ft\u0131rma<\/strong> i\u015flemi pek \u00e7ok alanda faydalan\u0131lan bir hesaplamal\u0131 kimya y\u00f6ntemidir. \u0130la\u00e7 ke\u015ffinde uygulanan ilk ad\u0131mlardan biri olarak g\u00f6ze \u00e7arpmaktad\u0131r. \u0130la\u00e7 Ke\u015fif \u00e7al\u0131\u015fmalar\u0131n\u0131n ilk ad\u0131m\u0131 olan <a href=\"https:\/\/www.ortaakarsu.net\/?p=6403\">bilgisayar destekli ila\u00e7 tasar\u0131m\u0131<\/a> molek\u00fcler <strong>yana\u015ft\u0131rma<\/strong> hesaplamalar\u0131n\u0131 i\u00e7ermektedir. Covid19 i\u00e7in geli\u015ftirilen ve\/veya yeniden ama\u00e7land\u0131r\u0131lan ila\u00e7lar da bu \u015fekilde hesaplamal\u0131 kimya y\u00f6ntemleri ile bulunmakta ve bu y\u00f6ntemler s\u0131kl\u0131kla kullan\u0131lmaktad\u0131r. <a href=\"https:\/\/www.ortaakarsu.net\/?p=6628\">Favicovir Kullananlar i\u00e7in Ayr\u0131nt\u0131l\u0131 \u0130nceleme<\/a> adl\u0131 yaz\u0131da a\u00e7\u0131kland\u0131\u011f\u0131 gibi protein-ligand etkile\u015fimleri hesaplanmaktad\u0131r. Bu yaz\u0131da ayr\u0131ca favicovir kullananlar i\u00e7in favicovir yan etkileri ile ilgili bilgilerde bulunmaktad\u0131r(yan etki bilgilerinin molek\u00fcler kenetlenme \u00e7al\u0131\u015fmalar\u0131 ile de\u011fil in vivo \u00e7al\u0131\u015fmalar ile elde edildi\u011fini unutmay\u0131n\u0131z).Bu konuda en iyi \u00f6rneklerden biri <a href=\"https:\/\/www.ortaakarsu.net\/?p=75\">Docking ve Kanser Tedavisinde Kullan\u0131m\u0131<\/a> adl\u0131 yaz\u0131daki \u00f6rneklerdir. <strong>Protein-ligand yana\u015ft\u0131rma<\/strong>, yani molek\u00fcler docking i\u015flemleri hesaplamal\u0131 kimyada ila\u00e7 ke\u015ffi i\u00e7in kullan\u0131lan ilk y\u00f6ntemlerdir. Bu ad\u0131mdan sonra sonu\u00e7lar\u0131n daha kesin olarak yorumlanmas\u0131 i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=6696\">Molek\u00fcler Dinamik Sim\u00fclasyonlar\u0131<\/a> adl\u0131 yaz\u0131da bahsedilen s\u00fcre\u00e7 uygulan\u0131r.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Yana\u015ft\u0131rma, yani molek\u00fcler docking (veya molek\u00fcler kenetlenme) pek \u00e7ok ad\u0131mdan  [&#8230;]<\/p>\n","protected":false},"author":1,"featured_media":6859,"comment_status":"open","ping_status":"open","sticky":false,"template":"single-hero-cover.php","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[6],"tags":[8,102,104,92,101,154,105,156,155],"class_list":["post-6856","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-molekuler-docking","tag-docking","tag-enzim-aktivitesi","tag-enzim-inhibisyonu","tag-enzimler","tag-glutatyon-reduktaz","tag-kenetlenme","tag-molekuler-docking","tag-protein-ligand-yanastirma","tag-yanastirma"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts\/6856","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=6856"}],"version-history":[{"count":0,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts\/6856\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/media\/6859"}],"wp:attachment":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=6856"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=6856"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=6856"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}