{"id":6696,"date":"2020-08-25T22:22:16","date_gmt":"2020-08-25T19:22:16","guid":{"rendered":"https:\/\/www.ortaakarsu.net\/?p=6696"},"modified":"2022-10-02T23:30:37","modified_gmt":"2022-10-02T20:30:37","slug":"molekuler-dinamik","status":"publish","type":"post","link":"https:\/\/www.ortaakarsu.net\/?p=6696","title":{"rendered":"Molek\u00fcler Dinamik Sim\u00fclasyonlar\u0131"},"content":{"rendered":"\n<h1 class=\"wp-block-heading\">Molek\u00fcler Dinamik Nedir?<\/h1>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<div class=\"video-shortcode\"><iframe title=\"An Introduction to Molecular Dynamics\" width=\"1200\" height=\"675\" src=\"https:\/\/www.youtube.com\/embed\/lLFEqKl3sm4?start=5&#038;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<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-4-3 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<div class=\"video-shortcode\"><iframe title=\"Molek\u00fcler Dinamik Sim\u00fclasyonunda Bir Ligand\u0131n Protein Yap\u0131 \u0130\u00e7erisinde Hareketi(PDB ID: 6AZP)\" width=\"1200\" height=\"900\" src=\"https:\/\/www.youtube.com\/embed\/iQC0NLP42bI?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\">Molek\u00fcler dinamik par\u00e7ac\u0131klar\u0131n hareketini incelemek i\u00e7in bilgisayar sim\u00fclasyon y\u00f6ntemleri kullan\u0131lmas\u0131d\u0131r. Newton&#8217;un hareket denklemini say\u0131sal olarak \u00e7\u00f6zme bu hesaplaman\u0131n temelini olu\u015fturmaktad\u0131r. Potansiyel enerji fonksiyonu ile y\u00f6nlenen par\u00e7ac\u0131klar\u0131n etkile\u015fimleri (kuvvet alan\u0131) hesaplaman\u0131n konusunu olu\u015fturur.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized is-style-default\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-34.png\" alt=\"molek\u00fcler dinamik par\u00e7ac\u0131klar\u0131n birbiri ile olan etkile\u015fimlerini hesaplar\" class=\"wp-image-6697\" width=\"338\" height=\"178\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-34-300x158.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-34.png 306w\" sizes=\"(max-width: 338px) 100vw, 338px\" \/><figcaption>Par\u00e7ac\u0131klar\u0131n her birinin bir biri ile olan etkile\u015fimi hesaplan\u0131r.<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Hesaplama i\u015fleminin sonucu, d\u0131\u015f ko\u015fullara ba\u011fl\u0131 olarak sistemin belli bir zaman aral\u0131\u011f\u0131nda ge\u00e7irdi\u011fi de\u011fi\u015fimin izlenmesidir. (e.g. pH 7, T = 300 K, p = 1 atm): trajectory<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized is-style-default\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-35.png\" alt=\"molek\u00fcler dinamik zamana ba\u011fl\u0131 olarak par\u00e7ac\u0131k hareketlerini inceler\" class=\"wp-image-6698\" width=\"335\" height=\"213\"\/><figcaption>Molek\u00fcler dinamik ile par\u00e7ac\u0131klar\u0131n durumlar\u0131 zamana ba\u011fl\u0131 olarak izlenir.<\/figcaption><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\">Molek\u00fcler Dinamik Sim\u00fclasyonlar\u0131 Teorik Arka Plan<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">MD sim\u00fclasyonu, biyolojik&nbsp;ve kimyasal&nbsp;makromolek\u00fcllerin dinamik davran\u0131\u015f\u0131n\u0131n teorik \u00e7al\u0131\u015fmalar\u0131nda&nbsp;ana ara\u00e7lardan biridir. Bu&nbsp;bilgisayarl\u0131&nbsp;hesaplama y\u00f6ntemi&nbsp;ile bir biyomolek\u00fcler sistemin zamana ba\u011fl\u0131 davran\u0131\u015f\u0131 hesaplan\u0131r. Atomlar, deney&nbsp;ve g\u00f6zlemlere dayanan&nbsp;potansiyel enerji fonksiyonlar\u0131&nbsp;veya \u00e7al\u0131\u015fma alan\u0131na ba\u011fl\u0131 olarak se\u00e7ilen \u00e7e\u015fitli kuvvet alanlar\u0131 kullan\u0131larak birbirleriyle etkile\u015fim&nbsp;i\u00e7ine girebilirler&nbsp;ve atomlara etki eden&nbsp;her&nbsp;kuvvetler, bu fonksiyonlara veya kuvvet alanlar\u0131na&nbsp;dayal\u0131 olarak belirli bir konfig\u00fcrasyon i\u00e7in hesaplan\u0131r. Newton&#8217;un hareket denkleminin (a\u015fa\u011f\u0131da g\u00f6sterilmi\u015ftir) entegrasyonuyla, sistemin belirli bir zaman aral\u0131\u011f\u0131&nbsp;boyunca ard\u0131\u015f\u0131k bir konfig\u00fcrasyonu elde edilir.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-43.png\" alt=\"\" class=\"wp-image-6864\" width=\"243\" height=\"144\"\/><figcaption>Newton&#8217;un Hareket Denklemi<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Burada Ri , <em>i <\/em>taneci\u011fin&nbsp;konumunu temsil eder ve&nbsp;Fi di\u011fer t\u00fcm molek\u00fcller taraf\u0131ndan uygulanan i par\u00e7ac\u0131\u011f\u0131na etki eden toplam kuvvet ve onun molek\u00fcler k\u00fctlesi&nbsp;mi \u2018dir. Molek\u00fcler dinamik ile ilgili yap\u0131lm\u0131\u015f farkl\u0131 bir akademik bir \u00e7al\u0131\u015fma <strong><a href=\"https:\/\/doi.org\/10.1021\/ci4002348\">American Chemical Society<\/a><\/strong>. Molek\u00fcler dinamik sim\u00fclasyonlar\u0131nda protein-ligand etkile\u015fimleri i\u00e7in bir \u00f6nceki ad\u0131m <a href=\"https:\/\/www.ortaakarsu.net\/?p=6856\">yana\u015ft\u0131rma<\/a> yani docking i\u015flemidir.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Molek\u00fcler Dinamik Kullan\u0131m Alanlar\u0131 ve Farkl\u0131 Ad\u0131mlar<\/h2>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"431\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36-1024x431.png\" alt=\"molek\u00fcler dinamik kullan\u0131m alanlar\u0131, i\u015fleyi\u015fi, farkl\u0131 ba\u011flamlar\u0131\" class=\"wp-image-6699\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36-300x126.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36-500x210.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36-550x232.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36-700x295.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36-768x323.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36-1024x431.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-36.png 1233w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>Molek\u00fcler dinamik pek \u00e7ok alanda kullan\u0131lmaktad\u0131r.<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Molek\u00fcler dinamik(MD)<\/strong> ila\u00e7 tasar\u0131m\u0131nda protein ve ligand yap\u0131 etkile\u015fimlerinin ili\u015fkisini \u00e7\u00f6z\u00fcmlemede de kullan\u0131lmaktad\u0131r. Bir protein yap\u0131ya kenetlenen yani <a href=\"https:\/\/www.ortaakarsu.net\/?p=6409\">molek\u00fcler docking<\/a> yap\u0131lan ligand\u0131n etkisi, bu y\u00f6ntemle desteklenerek daha kesin sonu\u00e7larla sunulur. Bu ila\u00e7 tasar\u0131m\u0131nda, etkili ila\u00e7 adaylar\u0131n\u0131n ay\u0131rt edilmesinde \u00f6nemli bir ad\u0131md\u0131r. <a href=\"https:\/\/www.ortaakarsu.net\/?p=6403\">Bilgisayar destekli ila\u00e7 tasar\u0131m\u0131<\/a> yaz\u0131s\u0131nda ila\u00e7 ke\u015ffinin farkl\u0131 ad\u0131mlar\u0131 da anlat\u0131lmaktad\u0131r.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"447\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38-1024x447.png\" alt=\"Molek\u00fcler Dinami\u011fin Farkl\u0131 Kullan\u0131m Alanlar\u0131\" class=\"wp-image-6753\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38-300x131.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38-500x218.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38-550x240.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38-700x305.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38-768x335.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38-1024x447.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-38.png 1243w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>Molek\u00fcler Dinami\u011fin Farkl\u0131 Kullan\u0131m Alanlar\u0131<\/figcaption><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\">Kuvvet Alan\u0131<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Kimyasal ba\u011flar\u0131n ve etkile\u015fimlerin,&nbsp;enerji baz\u0131nda&nbsp;hesaplanmas\u0131&nbsp;i\u00e7in hesaplamal\u0131&nbsp;kimyada matematiksel fonksiyonlar&nbsp;kullan\u0131l\u0131r. Hesaplamal\u0131 kimya ile analiz edilecek istemin potansiyel enerjisi, atomik konumlar\u0131n(koordinatlar\u0131n)&nbsp;bir fonksiyonu olarak kuvvet alanlar\u0131yla tan\u0131mlan\u0131r. \u015eekil 3&#8217;de g\u00f6r\u00fcld\u00fc\u011f\u00fc&nbsp;gibi, Molek\u00fcler Dinamik sim\u00fclasyonlar\u0131, ba\u011flar\u0131n gerilmesini, b\u00fck\u00fclmesini ve ayr\u0131ca ba\u011f&nbsp;yapmayan&nbsp;etkile\u015fimleri i\u00e7eren bir sistem i\u00e7indeki etkile\u015fimlerin deneysel olarak bulunmu\u015f matematik fonksiyonlar\u0131na&nbsp;g\u00f6re modellenmi\u015ftir.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large is-resized\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-44.png\" alt=\"Molek\u00fcler Dinamik Sim\u00fclasyonlar\u0131 i\u00e7in kuvvet alanlar\u0131\" class=\"wp-image-6865\" width=\"591\" height=\"298\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-44-300x152.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-44.png 499w\" sizes=\"(max-width: 591px) 100vw, 591px\" \/><figcaption>Molek\u00fcler Dinamik Sim\u00fclasyonlar\u0131 i\u00e7in Kuvvet Alanlar\u0131<\/figcaption><\/figure>\n<\/div>\n\n\n<p class=\"wp-block-paragraph\">Yukar\u0131daki fonksiyonda,&nbsp;V(R1,\u2026.,RN ) potansiyel enerjiyi temsil etmektedir&nbsp;ve bu, N &nbsp;tane atom veya par\u00e7ac\u0131\u011f\u0131n koordinatlar\u0131n\u0131n (Ri) &nbsp;\u015feklinde g\u00f6sterildi\u011fi bir fonksiyonudur. Denklemde, ilk terim, ba\u011f&nbsp;yapan&nbsp;atom \u00e7iftlerinin etkile\u015fimini temsil eder ve <em>li <\/em>, ba\u011f uzunlu\u011funun ifade edildi\u011fi terimdir. \u0130kinci terim Hooke Yasas\u0131n\u2019n\u0131n matematiksel ifadesidir&nbsp;ve harmonik potansiyel olarak modellenen molek\u00fcldeki&nbsp;ba\u011flar\u0131n&nbsp;a\u00e7\u0131lar\u0131n\u0131n&nbsp;toplam\u0131n\u0131 ifade eder, burada&nbsp;Qi&nbsp;ba\u011f\u0131n&nbsp;ilk&nbsp;andaki a\u00e7\u0131s\u0131n\u0131&nbsp;ve&nbsp;Qi,0&nbsp;ba\u011f\u0131n&nbsp;denge a\u00e7\u0131s\u0131n\u0131 ifade eder. Denklemde, \u00fc\u00e7\u00fcnc\u00fc terim burulma potansiyelini a\u00e7\u0131klar.&nbsp;D\u00f6rd\u00fcnc\u00fc denklem, iki farkl\u0131 potansiyel ile temsil edilen ba\u011f&nbsp;yapmayan&nbsp;etkile\u015fimleri temsil eder. \u0130lki, van der Waals etkile\u015fimlerini a\u00e7\u0131klayan LennardJones potansiyel fonksiyonudur, ikincisi ise elektrostatik etkile\u015fimler i\u00e7in Coulomb potansiyelidir.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u00d6rnek Bir \u00c7\u0131kt\u0131<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Protein yap\u0131ya kenetlenen ligand protein yap\u0131n\u0131n hereketini engelliyor ise bu protein i\u015flevini ger\u00e7ekle\u015ftiremez veya normalden daha az ger\u00e7ekle\u015ftirir hale geliyor demektir. Bu protein yap\u0131 bir resept\u00f6r veya enzin olabilir. A\u015fa\u011f\u0131daki videoda glutatyon red\u00fcktaz enziminin hareketi g\u00f6sterilmektedir. Bunun yan\u0131nda <a href=\"https:\/\/www.ortaakarsu.net\/?p=6606\">Raltegravir \u2013 \u0130ntegraz \u0130nhibit\u00f6rlerinin \u0130lki<\/a> adl\u0131 yaz\u0131da ba\u015fka bir molek\u00fcler docking \u00e7al\u0131\u015fmas\u0131 ayr\u0131nt\u0131l\u0131 olarak, ba\u011flanma modlar\u0131n\u0131 da i\u00e7ine alacak \u015fekilde incelendi. Bir enzim inhibisyon mekanizmas\u0131n\u0131n nas\u0131l i\u015fledi\u011fini anlamak i\u00e7in ideal yaz\u0131lardan biri.<\/p>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-4-3 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<div class=\"video-shortcode\"><iframe title=\"Glutatyon Red\u00fcktaz Enziminin Molek\u00fcler Dinamik \u00c7al\u0131\u015fmas\u0131 - \u0130nhibisyon\" width=\"1200\" height=\"900\" src=\"https:\/\/www.youtube.com\/embed\/CI06gU95wPk?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><figcaption>Glutatyon Red\u00fcktaz inhibisyonu molek\u00fcler dinamik sim\u00fclasyonu<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Bu g\u00f6r\u00fcnt\u00fc, enzimin hareketi ile inhibit\u00f6r bir ligand\u0131n kenetlendi\u011fi zamanki hareketini g\u00f6stermektedir. Protein yap\u0131 ile iyi inhibisyon yapan bir ligand kenetlendi\u011finde protein yap\u0131 substrat ile yapt\u0131\u011f\u0131 hareketinden daha farkl\u0131, daha &#8220;az&#8221; bir hareket yapacakt\u0131r. Bu MD sim\u00fclasyonlar\u0131n\u0131n de\u011ferlendirilmesi ve yorumlanmas\u0131nda temel prensiplerden birini olu\u015fturur.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">MD&#8217;nin \u0130la\u00e7 Geli\u015ftirme \u00c7al\u0131\u015fmalar\u0131mda \u00d6nemi<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130la\u00e7 geli\u015ftirme \u00e7al\u0131\u015fmalar\u0131 temelde yap\u0131 bazl\u0131 ve ligand bazl\u0131 olmak \u00fczere ikiye ayr\u0131lmaktad\u0131r. \u00d6zellikle yap\u0131 bazl\u0131 ila\u00e7 tasar\u0131m\u0131nda bir enzimi ve ya resept\u00f6r\u00fc inhibe edecek ligandlar belirlenir. Yani sanal taramas\u0131 yap\u0131lan k\u00fct\u00fcphanedeki ligandlar i\u00e7erisinde en iyi inhibisyonu yapmas\u0131 <strong>\u00f6ng\u00f6r\u00fclen<\/strong> ligandlar. Bu ligandlar protein yap\u0131ya kenetlendikten sonra inhibisyon b\u00f6lgesinde ne kadar s\u00fcreyle durdu\u011fu ve protein yap\u0131n\u0131n hareketinin ne \u00f6l\u00e7\u00fcde de\u011fi\u015fti\u011fine bak\u0131l\u0131r. En iyi kenetlenme puan\u0131na sahip ligandlar her zaman protein yap\u0131ya uzun s\u00fcre kenetli olarak durmamaktad\u0131r. Bu durum sadece kenetlenme puan\u0131na bakarak bir ila\u00e7 ke\u015ffinin yap\u0131lamayaca\u011f\u0131 anlam\u0131na gelir.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"470\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37-1024x470.png\" alt=\"Molek\u00fcler dinamik \u00e7al\u0131\u015fmalar\u0131n\u0131n kullan\u0131m alanlar\u0131ndan biri\" class=\"wp-image-6751\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37-300x138.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37-500x229.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37-550x252.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37-700x321.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37-768x352.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37-1024x470.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-37.png 1070w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>\u0130la\u00e7 Ke\u015ffi \u00c7al\u0131\u015fmalar\u0131nda Genel \u0130\u015f Ak\u0131\u015f\u0131 &#8211; Molek\u00fcler Dinamik \u00c7al\u0131\u015fmalar\u0131n\u0131n \u0130la\u00e7 Ke\u015ffinde Kullan\u0131m\u0131<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Koronavir\u00fcs salg\u0131n\u0131 ile m\u00fccadele etti\u011fimiz \u015fu g\u00fcnlerde ila\u00e7 ke\u015ffi i\u00e7in gerekli olan \u00e7al\u0131\u015fmalardan biri yine molek\u00fcler dinamik \u00e7al\u0131\u015fmlar\u0131d\u0131r. Covid-19 i\u00e7in ila\u00e7 ke\u015fif \u00e7al\u0131\u015fmalar\u0131nda favicovir ile ilgili pek \u00e7ok veri bulunmaktad\u0131r. Favicovir ektili bir RNA proteaz inhibit\u00f6r\u00fc olarak kar\u015f\u0131m\u0131za \u00e7\u0131kmakta. Favicovir ile ilgili daha \u00e7ok bilgi i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=6628\">Favicovir Yap\u0131s\u0131, Sentezi ve \u00d6zellikleri<\/a> adl\u0131 yaz\u0131y\u0131 okuyabilirsiniz. Bu g\u00fcn litarat\u00fcrde yer alan etkili olma ihtimali y\u00fcksek ila\u00e7lar\u0131n ke\u015fif ve yeniden ama\u00e7land\u0131rma \u00e7al\u0131\u015fmalar\u0131nda molek\u00fcler dinamik sim\u00fclasyonlar\u0131 da s\u0131kl\u0131kla kullan\u0131lmakta.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bir <strong>molek\u00fcler docking<\/strong> \u00e7al\u0131\u015fmas\u0131yla be\u015f ayr\u0131 iyi inhibit\u00f6r bulundu\u011funu varsayal\u0131m. Bu inhibit\u00f6rler i\u00e7erisinde birbirine \u00e7ok yak\u0131n kenetlenme puanlar\u0131 elde eden ligandlar olabilece\u011fi gibi kenetlenme puanlar\u0131 baz\u0131nda makas\u0131n a\u00e7\u0131lmas\u0131 da s\u00f6z konusu olabilir. Temel de\u011ferlendirmede bundan sonraki ad\u0131m ligandlar\u0131n protein yap\u0131da ne kadar s\u00fcre ile kald\u0131klar\u0131 ile ilgilidir. Kenetlenme puan\u0131 y\u00fcksek olan ligandlar\u0131n, protein yap\u0131ya kenetli kalma s\u00fcreleri genellikle daha uzundur. Ancak kenetlenme puan\u0131 d\u00fc\u015f\u00fck olan ligandlar\u0131n protein yap\u0131ya daha uzun s\u00fcre kenetli kalma ihtimalleri her zaman vard\u0131r. Zaten <strong>molek\u00fcler dinamik<\/strong> \u00e7al\u0131\u015fmalar\u0131n\u0131n yap\u0131lmas\u0131ndaki temel nedenlerden biri de budur. <\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Molek\u00fcler Dinamik Verileri ve Yorumlama<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Molek\u00fcler dinamik<\/strong> verilerinin yorumlanmas\u0131 i\u00e7in iki temel veri esas al\u0131n\u0131r. Bunlar <strong>RMSD<\/strong> ve <strong>RMSF <\/strong>grafikleridir. Bu grafiklerin haricinde pek \u00e7ok veriye de ula\u015f\u0131l\u0131r. Bu veriler spesifik konularda ara\u015ft\u0131rmac\u0131ya derinlemesine bilgiler vermektedirler. Bunlar\u0131n haricinde bir protein-ligand kenetlenmesinin de\u011ferlendirilmesinde RMSD ve RMSF de\u011ferleri genellikle yeterli bilgiyi ara\u015ft\u0131rmac\u0131ya sunmaktad\u0131r. RMSD ve RMSF verilerinin haricinde al\u0131nabilecek di\u011fer verilerin ba\u015f\u0131nda ba\u011f t\u00fcrlerinin ve etkile\u015fimlerinin zamanla de\u011fi\u015fimi(hidrofobik etkile\u015fimler, hidrojen ba\u011flar\u0131 ve bunun gibi), kenetlenen molek\u00fcl\u00fcn etkile\u015fim i\u00e7erisine girdi\u011fi amino asit kal\u0131nt\u0131lar\u0131n\u0131n zamana g\u00f6re de\u011fi\u015fimi, protein zincirindeki birincil ve ikincil yap\u0131lar\u0131n hareketi ba\u015fta gelmektedir. A\u015fa\u011f\u0131daki ligand\u0131n glutatyon red\u00fcktaz enzimine(<a href=\"https:\/\/www.rcsb.org\/structure\/3dk8\">PDB: 3DK8<\/a> <strong>DOI:&nbsp;<\/strong><a href=\"http:\/\/doi.org\/10.2210\/pdb3DK8\/pdb\" target=\"_blank\" rel=\"noreferrer noopener\">10.2210\/pdb3DK8\/pdb<\/a>) kenetlenmi\u015f halinin molek\u00fcler dinamik sim\u00fclasyonu \u00f6rnek olarak al\u0131nm\u0131\u015ft\u0131r ve bu sim\u00fclasyonun verileri anlat\u0131lm\u0131\u015ft\u0131r.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"1002\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-1024x1002.png\" alt=\"molek\u00fcler dinamik sim\u00fclasyonu yap\u0131lan ligand\" class=\"wp-image-6724\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-300x293.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-500x489.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-550x538.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-700x685.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-768x751.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-1024x1002.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main-1536x1502.png 1536w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L_2d_main.png 1600w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>Glutatyon Red\u00fcktaz enzimine molek\u00fcler docking ile kenetlenen ligand.<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">K\u00f6k Ortalama Kare Sapmas\u0131(RMSD) Nedir? Nas\u0131l Yorumlan\u0131r?<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Sim\u00fclasyon y\u00f6r\u00fcngesinin geri al\u0131nmas\u0131ndan sonra, protein (ve varsa ligand), zamana g\u00f6re hareketlerini nicel olarak analiz etmek i\u00e7in sistemden izole edilir. Y\u00f6r\u00fcnge \u00fczerinde yap\u0131lan ilk analiz, bir zaman ad\u0131m\u0131 al\u0131n\u0131r ve atomlar hareket ederken, omurgadaki protein alfa-Karbon atomlar\u0131n\u0131n ba\u015flang\u0131\u00e7 \u200b\u200bkoordinatlar\u0131na g\u00f6re k\u00f6k ortalama kare sapmas\u0131d\u0131r (RMSD). Bir ligand\u0131n ba\u011flanmas\u0131 \u00fczerine omurga C(alfa) atomlar\u0131n\u0131n hareket serbestli\u011finde bir engel olmas\u0131 beklenir. Bu, enzimin ba\u011flanma bo\u015flu\u011funun serbest\u00e7e hareket edemeyece\u011fi, aktivitesini kaybedece\u011fi ve i\u015flevin engellendi\u011fi anlam\u0131na gelir. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu ama\u00e7la dimerik proteinin B zincirinin omurga C(alfa) atomlar\u0131n\u0131n RMSD de\u011ferleri d\u0131\u015far\u0131dan al\u0131nm\u0131\u015f ve zamana kar\u015f\u0131 grafi\u011fe ge\u00e7irilmi\u015ftir. Bu ad\u0131m, B zincirinin hem apo hem de holo formlar\u0131 i\u00e7in ger\u00e7ekle\u015ftirilir(birden fazla zincir olmas\u0131 durumunda). Elde edilen grafikler, s\u00f6z konusu zincirin enzimin hem apo hem de holo formlar\u0131ndaki hareketini anlamaya y\u00f6nelik netlik i\u00e7in tek alan \u00fczerinde sunulur. Ligand\u0131n zamana g\u00f6re hareketi de \u015fekilde g\u00f6sterilen grafi\u011fe dahil edilmi\u015ftir. A\u015fa\u011f\u0131daki \u015fekilde(grafik-1 ve grafik-2) g\u00f6sterilen birimler, \u00c5ngstromlar olarak sunulmu\u015ftur ve de\u011ferler, proteinlerde veya ligandlarda farkl\u0131 \u015fekilde se\u00e7ilen belirli atomlar\u0131n g\u00f6receli hareketinin g\u00f6zlenmesine dayanak olu\u015fturur. Proteinler i\u00e7in, k\u00f6k ortalama kare sapmalar\u0131n\u0131n hesaplanmas\u0131 i\u00e7in alfa Karbonlar se\u00e7ilir. Ligand molek\u00fclleri i\u00e7in, omurga atomlar\u0131 genellikle ayn\u0131 ama\u00e7 i\u00e7in se\u00e7ilir.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Hesaplaman\u0131n \u00d6zellikleri ve Hesaplama S\u00fcresi<\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Grafiklerin yorumlanmas\u0131 a\u015fa\u011f\u0131daki \u00f6rnek grafik ile yap\u0131lacakt\u0131r. Bu grafik 1,2 nano saniyelik bir hesaplama s\u00fcresi ile \u00e7izilmi\u015ftir. Bunun anlam\u0131 ligand\u0131n protein yap\u0131ya kenetlendi\u011fi andan sonraki 1,2 nano saniye i\u00e7erisinde neler oldu\u011funun t\u00fcm atomlar baz\u0131nda hesaplanmas\u0131, hareketlerinin grafi\u011fe ge\u00e7irilmesi ve \u00e7e\u015fitli etkile\u015fimlerin ger\u00e7ekle\u015fme durumlar\u0131na ayr\u0131nt\u0131s\u0131yla bak\u0131lmas\u0131 anlam\u0131na gelir. 1,2 nano saniyenin son derece k\u0131sa bir hesaplama aral\u0131\u011f\u0131 oldu\u011fu unutulmamal\u0131d\u0131r. Litarat\u00fcrde 700 nano saniyeye kadar molek\u00fcler dinamik hesaplamalar\u0131 yap\u0131lmaktad\u0131r. Bu veriler \u00f6rnek olarak sunulmu\u015ftur. Hesaplama s\u00fcresinin litarat\u00fcr i\u00e7in ge\u00e7erli bir s\u00fcre olmas\u0131 elde edilen RMSD de\u011ferlerinin uygun bir plato olu\u015fturmas\u0131, yani belirli aral\u0131klardan d\u0131\u015far\u0131 \u00e7\u0131kmamas\u0131 \u015feklinde ifade edilir. Bu belirli aral\u0131k iyi inhibe eden bir ligand i\u00e7in 3 \u00c5ngstromlar civar\u0131d\u0131r ve olabildi\u011fince 0&#8217;a yak\u0131n olmas\u0131 istenir. Bu olas\u0131 plato seviyelerinin olu\u015fmas\u0131 i\u00e7in gerekli hesaplama s\u00fcresi genelde 50 ns civarlar\u0131d\u0131r. Ancak hesaplama s\u00fcresinin daha da uzun tutulmas\u0131 her zaman daha ge\u00e7erli bir \u00e7al\u0131\u015fma ortaya \u00e7\u0131kmas\u0131n\u0131 sa\u011flayacakt\u0131r. <\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"755\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-1024x755.png\" alt=\"Molek\u00fcler dinamik verilerinden RMSD de\u011ferlerini g\u00f6steren grafik\" class=\"wp-image-6720\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-300x221.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-500x368.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-550x405.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-700x516.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-768x566.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-1024x755.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-RMSD-1536x1132.png 1536w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption><strong>Grafik-1<\/strong>: Glutatyon Reduktaz enzimine yap\u0131lan bir kenetlenme yani docking \u00e7al\u0131\u015fmas\u0131 i\u00e7in ger\u00e7ekle\u015ftirilen molek\u00fcler dinamik hesaplamas\u0131n\u0131n RMSD Grafi\u011fi.<\/figcaption><\/figure>\n\n\n\n<h4 class=\"wp-block-heading\">Protein RMSD nedir? <\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Yukar\u0131daki grafik, bir proteinin (sol Y ekseni) RMSD evrimini g\u00f6stermektedir. T\u00fcm protein \u00e7er\u00e7eveleri \u00f6nce referans \u00e7er\u00e7eve omurgas\u0131 \u00fczerinde hizalan\u0131r ve ard\u0131ndan RMSD, atom se\u00e7imine g\u00f6re hesaplan\u0131r. Proteinin RMSD&#8217;sini izlemek, sim\u00fclasyon boyunca yap\u0131sal konformasyonuna ili\u015fkin i\u00e7g\u00f6r\u00fc sa\u011flayabilir. RMSD analizi, sim\u00fclasyonun dengelenip dengelenmedi\u011fini g\u00f6sterebilir. 1-3 \u00c5 s\u0131ras\u0131ndaki de\u011fi\u015fiklikler, k\u00fc\u00e7\u00fck, k\u00fcresel proteinler i\u00e7in m\u00fckemmel \u015fekilde kabul edilebilir. Bununla birlikte, bundan \u00e7ok daha b\u00fcy\u00fck de\u011fi\u015fiklikler, proteinin sim\u00fclasyon s\u0131ras\u0131nda b\u00fcy\u00fck bir konformasyonel de\u011fi\u015fikli\u011fe u\u011frad\u0131\u011f\u0131n\u0131 g\u00f6sterir. Sim\u00fclasyonunuzun yak\u0131nsamas\u0131 da \u00f6nemlidir &#8211; RMSD de\u011ferleri sabit bir de\u011fer etraf\u0131nda stabilize olur. Sim\u00fclasyonun sonunda proteinin RMSD&#8217;si ortalama olarak hala art\u0131yor veya azal\u0131yorsa, sisteminiz dengelenmemi\u015ftir ve sim\u00fclasyonunuz titiz analiz i\u00e7in yeterince uzun olmayabilir.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Ligand RMSD nedir? <\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Ligand RMSD (sa\u011f Y ekseni), ligand\u0131n proteine \u200b\u200bve bunun ba\u011flanma cebine g\u00f6re ne kadar stabil oldu\u011funu g\u00f6sterir. Yukar\u0131daki grafikte &#8220;Lig fit Prot&#8221;, protein-ligand kompleksi ilk olarak referans\u0131n protein omurgas\u0131 \u00fczerinde hizaland\u0131\u011f\u0131nda ve ard\u0131ndan ligand a\u011f\u0131r atomlar\u0131n\u0131n RMSD&#8217;si \u00f6l\u00e7\u00fcld\u00fc\u011f\u00fcnde bir ligand\u0131n RMSD&#8217;sini g\u00f6sterir. G\u00f6zlenen de\u011ferler proteinin RMSD&#8217;sinden \u00f6nemli \u00f6l\u00e7\u00fcde daha b\u00fcy\u00fckse, ligand\u0131n ba\u015flang\u0131\u00e7taki ba\u011flanma b\u00f6lgesinden uza\u011fa yay\u0131lm\u0131\u015f olmas\u0131 muhtemeldir.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">RMSD ve RMSF De\u011ferlerinin Yorumlanmas\u0131<\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Proteininin yap\u0131s\u0131ndaki konformasyonel de\u011fi\u015fimlerin ligand\u0131n varl\u0131\u011f\u0131 <strong>(holo form)<\/strong> ve yoklu\u011funda <strong>(apo form)<\/strong> k\u0131yaslanabilmesi RMSD ve RMSF de\u011ferlerini aras\u0131nda k\u0131yaslama yap\u0131lmas\u0131 verilerin de\u011ferlendirilmesindeki temeli olu\u015fturur. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Grafik-1<\/strong>&#8216;de a\u00e7\u0131k\u00e7a g\u00f6sterildi\u011fi gibi, enzimin omurgas\u0131n\u0131n zamana kar\u015f\u0131 sapmas\u0131 ligand\u0131n sokulmas\u0131yla engellenir. Apo formundaki omurga atomlar\u0131n\u0131n ortalama RMSD de\u011ferleri 4,89 \u00c5 ve holo formunda 2,68 \u00c5&#8217;dir. Bu, apo formundaki kal\u0131nt\u0131lar\u0131n serbest hareketinin, ligand\u0131n ba\u011flanmas\u0131 \u00fczerine enzim boyunca inhibe edildi\u011fini g\u00f6sterir. <\/p>\n\n\n\n<h3 class=\"wp-block-heading\">K\u00f6k Ortalama Kare Dalgalanmas\u0131(RMSF) Nedir? Nas\u0131l Yorumlan\u0131r?<\/h3>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"768\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-1024x768.png\" alt=\"\" class=\"wp-image-6721\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-300x225.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-500x375.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-550x413.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-700x525.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-768x576.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-1024x768.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF-1536x1152.png 1536w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF.png 1920w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption><strong>Grafik-2<\/strong>: Bir L1 ligand\u0131 i\u00e7in RMSF grafi\u011fi.<\/figcaption><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"768\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-1024x768.png\" alt=\"\" class=\"wp-image-6722\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-300x225.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-500x375.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-550x413.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-700x525.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-768x576.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-1024x768.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4-1536x1152.png 1536w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/P-RMSF_L4.png 1920w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption><strong>Grafik-3<\/strong>: L4 ligand\u0131 i\u00e7in RMSF grafi\u011fi<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Yukar\u0131daki iki grafik (Grafik-2 ve Grafik-3) ayn\u0131 protein yap\u0131ya kenetlenen iki ayr\u0131 ligand\u0131n RMSF grafi\u011fidir. Bu iki grafi\u011fi bir biri ile kar\u015f\u0131la\u015ft\u0131rarak hangi ligand\u0131n daha iyi inhihisyon yapt\u0131\u011f\u0131n\u0131 g\u00f6rmek m\u00fcmk\u00fcnd\u00fcr.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Molek\u00fcler dinamik sim\u00fclasyonlar\u0131n\u0131n ikinci analiz y\u00f6ntemi, k\u00f6k ortalama kare dalgalanmas\u0131 (RMSF) olarak adland\u0131r\u0131l\u0131r ve dalgalanma hakk\u0131nda bilgi verir. proteini olu\u015fturan bireysel kal\u0131nt\u0131lar\u0131n (veya hareketi). \u0130ki k\u00f6k ortalama kare hesaplamas\u0131 aras\u0131ndaki fark, RMSF&#8217;nin bir zaman ortalamas\u0131 olarak hesaplanmas\u0131 ve di\u011fer yandan, RMSD&#8217;nin her zaman ad\u0131m\u0131 i\u00e7in hesaplanmas\u0131d\u0131r. \u0130deal bir MD sim\u00fclasyonu durumunda, hedefin ikincil yap\u0131lar\u0131 olu\u015fturan kal\u0131nt\u0131lar\u0131 (kal\u0131nt\u0131lar aras\u0131ndaki hidrojen ba\u011f\u0131 etkile\u015fimleriyle olu\u015fturulan stabil yap\u0131lara sahip protein b\u00f6lgeleridir), aktif b\u00f6lgesinde bir inhibit\u00f6r bulundu\u011funda daha az dalgalan\u0131r.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">\u00d6rnek Analizi<\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Grafik-2 ve Grafik-3&#8217;\u00fc kar\u015f\u0131la\u015ft\u0131rd\u0131\u011f\u0131m\u0131zda grafikte pik yapan yerlere bakmam\u0131z gerekmektedir.  Molek\u00fcler dinamik sim\u00fclasyonunda Grafik-3&#8217;\u00fcn pik yapan alanlar\u0131 a\u00e7\u0131k\u00e7a daha fazla iken Grafik-2&#8217;de bu pik yapan bu alanlar azalm\u0131\u015ft\u0131r. Bu da Grafik-2&#8217;deki ligand\u0131n, yani L1 ligand\u0131n\u0131n, L4 ligand\u0131ndan daha iyi inhibisyon yapt\u0131\u011f\u0131n\u0131 g\u00f6sterir. Bu yorumlama \u015fekli protein yap\u0131n\u0131n apo formunda da ayn\u0131 \u015fekilde kullan\u0131labilir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu grafiklere bakt\u0131\u011f\u0131m\u0131zda pik alanlar\u0131 ve plato alanlar\u0131 g\u00f6r\u00fclmekte bunun nedeni bu grafiklerde zirve olarak g\u00f6r\u00fcnen yerler, sim\u00fclasyon zaman aral\u0131\u011f\u0131 i\u00e7erisinde en \u00e7ok dalgalanma g\u00f6steren protein alanlar\u0131n\u0131 g\u00f6sterir.  Burada kuyruk k\u0131s\u0131mlar\u0131 olarak tabir edebilece\u011fimiz (N- ve C-terminalleri de denilir) protein yap\u0131n\u0131n di\u011fer herhangi bir b\u00f6l\u00fcm\u00fcnden daha fazla dalgaland\u0131\u011f\u0131n\u0131 g\u00f6zlemlemek m\u00fcmk\u00fcnd\u00fcr. Alfa sarmal k\u0131s\u0131mlar\u0131 ve beta sarmal k\u0131s\u0131mlar\u0131 gibi ikincil yap\u0131 \u00f6geleri genellikle proteinin yap\u0131land\u0131r\u0131lmam\u0131\u015f k\u0131sm\u0131ndan daha serttir ve bu nedenle d\u00f6ng\u00fc b\u00f6lgelerinden daha az dalgalan\u0131r. <strong>Molek\u00fcler dinamik<\/strong> sim\u00fclasyonlar\u0131n\u0131n temel yorumlamas\u0131 bu \u015fekilde yap\u0131lmaktad\u0131r.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Molek\u00fcler Dinamik Sim\u00fclasyonunda Di\u011fer Veriler<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Ligand ile protein etkile\u015fimleri sim\u00fclasyon boyunca izlenebilir. Bu etkile\u015fimler, yukar\u0131daki grafikte g\u00f6sterildi\u011fi gibi t\u00fcre g\u00f6re kategorize edilebilir ve \u00f6zetlenebilir. Protein-ligand etkile\u015fimleri (veya &#8216;temaslar\u0131&#8217;) d\u00f6rt tipte kategorize edilir: Hidrojen Ba\u011flar\u0131, Hidrofobik, \u0130yonik ve Su K\u00f6pr\u00fcleri. Her etkile\u015fim t\u00fcr\u00fc, &#8216;Sim\u00fclasyon Etkile\u015fim \u015eemas\u0131&#8217; paneli arac\u0131l\u0131\u011f\u0131yla ke\u015ffedilebilecek daha spesifik alt t\u00fcrler i\u00e7erir. Y\u0131\u011f\u0131nl\u0131 \u00e7ubuk grafikler, y\u00f6r\u00fcnge boyunca normalle\u015ftirilir: \u00f6rne\u011fin, 0,7 de\u011feri, sim\u00fclasyon s\u00fcresinin% 70&#8217;inin spesifik etkile\u015fimin korundu\u011funu g\u00f6sterir. 1.0&#8217;\u0131n \u00fczerindeki de\u011ferler m\u00fcmk\u00fcnd\u00fcr, \u00e7\u00fcnk\u00fc baz\u0131 protein art\u0131klar\u0131, ligand ile ayn\u0131 alt tipte birden fazla temas kurabilir.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"768\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-1024x768.png\" alt=\"Molek\u00fcler dinamik ligand ve protein etkile\u015fimleri\" class=\"wp-image-6723\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-300x225.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-500x375.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-550x413.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-700x525.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-768x576.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-1024x768.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram-1536x1152.png 1536w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Histogram.png 1920w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>Bir molek\u00fcler dinamik sim\u00fclasyonunda protein ligand etkile\u015fimleri ve bunlar\u0131n zamana ba\u011fl\u0131 olara nas\u0131l de\u011fi\u015fti\u011fi izlenebilir. <strong>A\u00e7\u0131k mavi hidrofobikk etkile\u015fimleri, koyu mavi su k\u00f6pr\u00fclerini g\u00f6stermektedir<\/strong>.<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Amino Asitlerle \u0130li\u015fkinin Zamana G\u00f6re De\u011fi\u015fimi<\/h3>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"768\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-1024x768.png\" alt=\"Molek\u00fcler dinamik sim\u00fclasyonu s\u0131ras\u0131nda ligand ile amino asit kal\u0131nt\u0131lar\u0131n\u0131n bir biri ile kurmu\u015f oldu\u011fu konta\u011f\u0131n grafiksel g\u00f6sterimi\" class=\"wp-image-6729\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-300x225.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-500x375.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-550x413.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-700x525.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-768x576.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-1024x768.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline-1536x1152.png 1536w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/PL-Contacts_Timeline.png 1920w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>Molek\u00fcler dinamik sim\u00fclasyonu s\u0131ras\u0131nda ligand ile amino asit kal\u0131nt\u0131lar\u0131n\u0131n bir biri ile kurmu\u015f oldu\u011fu konta\u011f\u0131n grafiksel g\u00f6sterimi<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Yukar\u0131daki grafik glutatyon red\u00fcktaz enzimine kenetlenen yani molek\u00fcler docking \u00e7al\u0131\u015fmas\u0131 yap\u0131lan bir ligand\u0131n hangi amino asit kal\u0131nt\u0131lar\u0131 ile etkile\u015fim yapt\u0131\u011f\u0131n\u0131 ve bu etkile\u015fimlerin \u015fiddetini g\u00f6stermektedir. Grafikte g\u00f6r\u00fcld\u00fc\u011f\u00fc gibi ligand\u0131m\u0131z en \u00e7ok 67. lisin ve 340. prolin amino asit kal\u0131nt\u0131lar\u0131 ile etkile\u015fime girmi\u015ftir. Bu etkile\u015fimlerin zamana ba\u011fl\u0131 de\u011fi\u015fimi de ayr\u0131ca g\u00f6sterilmi\u015ftir. Yine grafikten a\u00e7\u0131k\u00e7a g\u00f6r\u00fclece\u011fi gibi 67. lisin ve 340. prolin amino asit kal\u0131nt\u0131lar\u0131 sim\u00fclasyon zaman\u0131 boyunca olduk\u00e7a kuvvetli etkile\u015fim i\u00e7erisinde kalm\u0131\u015ft\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">372. amino asit olan fenilalanin ile de zamana g\u00f6re etkisi artan ve sonra azalan bir etkile\u015fim s\u00f6z konusu oldu\u011fu g\u00f6r\u00fclmektedir. 442. amino asit olan glutamin ile de yine zamanla de\u011fi\u015fen hafif bir etkile\u015fim g\u00f6r\u00fclmektedir. Bu \u00e7al\u0131\u015fman\u0131n molek\u00fcler dinamik sim\u00fclasyonundan sonra in vitro \u00e7al\u0131\u015fmas\u0131 yap\u0131lm\u0131\u015f ve yine L1 ligand\u0131n\u0131n olduk\u00e7a etkili bir inhibit\u00f6r oldu\u011fu g\u00f6r\u00fclerek molek\u00fcler dinamik sim\u00fclasyonlar\u0131n\u0131n olduk\u00e7a kesin bir \u015fekilde do\u011fru oldu\u011fu sonucuna var\u0131lm\u0131\u015ft\u0131r. Glutatyon red\u00fcktaz\u0131n in vitro \u00e7al\u0131\u015fmas\u0131 i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=95\">Glutatyon Red\u00fcktaz Enzim Aktivitesi<\/a> yaz\u0131m\u0131 okuyunuz. T\u00fcm bu de\u011ferlendirmeler molek\u00fcler dinamik i\u00e7in RMSD ve RMSF de\u011ferlerinin yan\u0131nda destekleyici veriler olarak g\u00f6r\u00fclmeli ve b\u00fct\u00fcn olarak de\u011ferlendirilmelidir.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Torsiyon A\u00e7\u0131lar\u0131(Zamanla De\u011fi\u015fim)<\/h3>\n\n\n\n<figure class=\"wp-block-image size-large is-style-default\"><img decoding=\"async\" width=\"1024\" height=\"768\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-1024x768.png\" alt=\"Sim\u00fclasyonlar\u0131nda torsiyon a\u00e7\u0131lar\u0131n\u0131n de\u011fi\u015fimi\" class=\"wp-image-6756\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-300x225.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-500x375.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-550x413.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-700x525.png 700w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-768x576.png 768w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-1024x768.png 1024w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions-1536x1152.png 1536w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/L-Torsions.png 1920w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>Torsiyon A\u00e7\u0131lar\u0131n\u0131n De\u011fi\u015fimi<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Ligandda yer alan, d\u00f6nebilen yer ba\u011f, protein kenetlenmesi ve sonras\u0131nda <strong>molek\u00fcler dinamik<\/strong> sim\u00fclasyonlar\u0131 s\u0131ras\u0131nda belirli a\u00e7\u0131larda d\u00f6ner. Bu da di\u011fer veriler gibi sim\u00fclasyon s\u00fcresi boyunca izlenebilir. Yukar\u0131da torsiyon a\u00e7\u0131lar\u0131n\u0131n hangi a\u00e7\u0131larda de\u011fi\u015fti\u011fi yani sim\u00fclasyon boyunca y\u00f6nlenmenin miktar\u0131 a\u00e7\u0131 cinsinden g\u00f6r\u00fclmektedir. Her renk ligandda bulunan bir ba\u011f\u0131 i\u015faret etmektedir. Ligand\u0131n hangi a\u00e7\u0131ya ne kadar zorland\u0131\u011f\u0131(kenetlendi\u011fi protein yap\u0131n\u0131n ve \u00e7\u00f6z\u00fcc\u00fcn\u00fcn etkisi ile) g\u00f6r\u00fclmekte ve grafi\u011fe ge\u00e7irilmektedir. Favicovir gibi koronavir\u00fcs i\u00e7in etkili olan ila\u00e7lar da ayn\u0131 \u015fekilde yeniden ama\u00e7land\u0131rma i\u015flemi ve molek\u00fcler <a href=\"https:\/\/www.ortaakarsu.net\/?p=6628\">yak\u0131nla\u015ft\u0131rma<\/a> i\u015flemine tabi tutulmaktad\u0131rlar. Ak\u0131ll\u0131 malzemelerin nas\u0131l elde edildi\u011fini \u00f6\u011frenmek i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=6996\">Elastomer, Elektroreolojik Elastomer ve \u00d6zellikleri<\/a> adl\u0131 yaz\u0131y\u0131 okuyabilirsiniz.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Molek\u00fcler Dinamik Nedir? Molek\u00fcler dinamik par\u00e7ac\u0131klar\u0131n hareketini incelemek i\u00e7in bilgisayar  [&#8230;]<\/p>\n","protected":false},"author":1,"featured_media":6397,"comment_status":"open","ping_status":"open","sticky":false,"template":"single-hero-cover.php","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[7],"tags":[97,101,143,106,9,146],"class_list":["post-6696","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-molekuler-dinamik","tag-bilgisayar-destekli-ilac-tasarimi","tag-glutatyon-reduktaz","tag-ilac-gelistirme","tag-ilac-kesfi","tag-ilac-tasarimi","tag-molekuler-dinamik"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts\/6696","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=6696"}],"version-history":[{"count":1,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts\/6696\/revisions"}],"predecessor-version":[{"id":8147,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts\/6696\/revisions\/8147"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/media\/6397"}],"wp:attachment":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=6696"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=6696"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=6696"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}