HIV-1 ters transkriptaz ve integraz enzimleri için ikili inhibitör tasarımı: Docking çalışması
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Tarih
2019-08-06
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Batman Üniversitesi Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Attribution-ShareAlike 3.0 United States
Attribution-ShareAlike 3.0 United States
Özet
Retrovirüslerin lentivürüs ailesi üyesi olan HIV-1 AIDS hastalığının etken virüsüdür. Virüs dünya çapında yaygın olup insan bağışıklık sistemini baskılayarak vücudu enfeksiyonlara karşı savunmasız bırakır. HIV-1 Ters Transkriptaz (Revers Transcriptase;RT) ve İntegraz (Integrase;IN) virüs yaşam döngüsünün önemli işlevlerini yerine getiren iki enzimdir. AIDS tedavisinde son yıllarda birden fazla hedefi inhibe eden ilaçların tasarımı üzerinde çalışılmaya başlanmıştır. Bu bakımdan, RT ve IN dual inhibitör geliştirilmesi bakımından uygun iki enzimdir. Bu çalışmada tasarlanan 858 ligand filtrelenerek ilaç olma özelliği olan 426 ligand Autodock4 programı ile bir RT kristal yapısı olan 4g1q.pdb ve tam uzunluktaki HIV-1 IN kristal yapısı bulunmadığından katalitik bölge açısından aynı özellikleri taşıyan Prototype Foamy Virus IN kristal yapısı 3oya.pdb aktif bölgelerine yerleştirildi. Yerleştirme sonucunda B099 ligandı -12.63 kcal/mol’lük skor ile RT enzimine ve B249 ligandı -19.83 kcal/mol’lük skor ile IN enzimine en iyi bağlanan ligandlar olarak belirlendi. B051, B053, B099, B103, B107, B205, B206, B211, B213, B223, B231,B241, B242, B249, B250, B251, B253, B254, B308, B324, B352 ve B353 ligandlarının her iki enzim için iyi yerleşme skorları verdiği gözlendi. Sonuç olarak dual inhibitör adayı olan yeni ligandların tasarımı gerçekleştirildi
HIV-1, a member of Retroviruses’ Lentivirus family, is the causative agent of AIDS. The virus is common throughout the world and leaves the body vulnerable to infections by suppressing the human immune system. Reverse Transcriptase (RT) and Integrase (IN) are two HIV-1 enzymes which perform important virus life cycle functions. It has been started to design new drug design that inhibit multiple targets for treatment of AIDS in recent years. In respect to this, RT and IN are two enzymes suitable for the development of dual inhibitors. 426 ligands which are filtered by druggability properties from 858 ligands were docked to crystal structure of 4g1q.pdb and since there was no full-lenght structure of HIV-1 IN same ligands were docked to Prototype Foamy Virus (PFV) IN structure 3oya.pdb, which have same properties as HIV-1 IN catalyctic region by Autodock4 program. From the docking results B099 ligand was determined to be the best binding ligand to RT ezyme with a binding score of -12.63 kcal/mol and B249 was the best ligand to IN enzyme with a score of -19.83 kcal/mol. B051, B053, B099, B103, B107, B205, B206, B211, B213, B223, B231,B241, B242, B249, B250, B251, B253, B254, B308, B324, B352 and B353 were found to give good docking scores for both enzymes. As a result, the design of new ligands, which are dual inhibitor candidates, was realized.
HIV-1, a member of Retroviruses’ Lentivirus family, is the causative agent of AIDS. The virus is common throughout the world and leaves the body vulnerable to infections by suppressing the human immune system. Reverse Transcriptase (RT) and Integrase (IN) are two HIV-1 enzymes which perform important virus life cycle functions. It has been started to design new drug design that inhibit multiple targets for treatment of AIDS in recent years. In respect to this, RT and IN are two enzymes suitable for the development of dual inhibitors. 426 ligands which are filtered by druggability properties from 858 ligands were docked to crystal structure of 4g1q.pdb and since there was no full-lenght structure of HIV-1 IN same ligands were docked to Prototype Foamy Virus (PFV) IN structure 3oya.pdb, which have same properties as HIV-1 IN catalyctic region by Autodock4 program. From the docking results B099 ligand was determined to be the best binding ligand to RT ezyme with a binding score of -12.63 kcal/mol and B249 was the best ligand to IN enzyme with a score of -19.83 kcal/mol. B051, B053, B099, B103, B107, B205, B206, B211, B213, B223, B231,B241, B242, B249, B250, B251, B253, B254, B308, B324, B352 and B353 were found to give good docking scores for both enzymes. As a result, the design of new ligands, which are dual inhibitor candidates, was realized.
Açıklama
Anahtar Kelimeler
Bilgisayar Destekli İlaç Tasarımı, Dual Inhibitor, HIV-1, İntegraz, Moleküler Yerleştirme, Ters Transkriptaz, Computer Aidded Drug Design, Dual Inhibitor, Integrase, Molecular Docking, Reverse Transcriptase
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Şenyiğit, B. (2019). HIV-1 ters transkriptaz ve integraz enzimleri için ikili inhibitör tasarımı: Docking çalışması. (Yayınlanmamış Yüksek Lisans Tezi). Batman Üniversitesi Fen Bilimleri Enstitüsü, Batman.
