Molecular Docking Analysis of Used Drugs for the Treatment of Cancer

Abstract

In this study, the lowest energy molecular structures were determined by conformational analysis of six drugs commonly used in cancer treatment, in order to use as initial data for docking simulations. Using the AutoDock Vina software, the interaction mechanisms of the 6 FDA approved drugs (Pemetrexed, Irinotecan, Tamoxifen, Gemcitabine, Topotecan and Temozolomide) with DNA were investigated. In addition, MM/PB(GB)SA calculations for the drug-DNA structures under investigation have been performed. The calculated binding affinities and binding free energies of interactions were showed the stability of the structures. It has been found that the active site where these molecules interact with DNA is the same and that their various interactions, primarily hydrogen bond, play an important role in this stability of the structures. Furthermore, the pharmacophoric features of the investigated molecules were determined.The aim of the work is to deeply investigate the binding properties of the title drugs with DNA.

Keywords

• Cancer
• Drugs
• Molecular modeling
• Conformational analysis
• Molecular docking

Kanser Tedavisinde Kullanılan İlaçların Moleküler Kenetlenme Analizi

Abstract

Bu çalışmada, kenetlenme simülasyonları için başlangıç verileri olarak kullanılmak üzere, kanser tedavisinde yaygın olarak kullanılan altı ilacın konformasyonel analizi ile en düşük enerjili moleküler yapıları belirlenmiştir. AutoDock Vina programı kullanılarak FDA onaylı 6 ilacın (Pemetrekset, Irinotekan, Tamoksifen, Gemsitabin, Topotekan ve Temozolomid) DNA ile etkileşim mekanizmaları araştırılmıştır. Ek olarak, araştırılan ilaç-DNA yapıları için MM/PB(GB)SA hesaplamaları yapılmıştır. Etkileşimlere ait hesaplanan bağlanma afiniteleri ve bağlanma serbest enerjileri yapıların kararlılığını göstermiştir. Bu moleküllerin DNA ile etkileştiği aktif bölgenin aynı olduğu ve başta hidrojen bağı olmak üzere yapmış oldukları çeşitli etkileşimlerin yapıların bu kararlılığında önemli bir rol oynadığı bulunmuştur. Ayrıca, incelenen moleküllerin farmokofor özellikleri belirlenmiştir. Bu çalışmanın amacı, başlıktaki ilaçların DNA ile bağlanma özelliklerini derinlemesine araştırmaktır.

Keywords

• Kanser
• İlaçlar
• Moleküler modelleme
• Konformasyon analizi
• Moleküler kenetlenme

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