کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1362619 981492 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A combined approach of docking and 3D QSAR study of β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
A combined approach of docking and 3D QSAR study of β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors
چکیده انگلیسی

The enzyme FabH catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase. The pivotal role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of antibacterial and antiparasitic compounds. Three-dimensional quantitative structure–activity relationship (3D QSAR) studies such as comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) and docking simulations were conducted on a series of potent benzoylaminobenzoic acids. Docking studies were employed to position the inhibitors into the FabH active site to determine the probable binding conformation. A reasonable correlation between the predicated binding free energy and the inhibitory activity was found. CoMFA and CoMSIA were performed based on the docking conformations, giving q2 of 0.637 and 0.697 for CoMFA and CoMSIA models, respectively. The predictive ability of the models was validated using a set of compounds that were not included in the training set and progressive scrambling test. Mapping the 3D QSAR models to the active site of FabH related that some important amino acid residues are responsible for protein–inhibitor interaction. These results should be applicable to the prediction of the activities of new FabH inhibitors, as well as providing structural understanding.

We performed CoMFA and CoMSIA based on the docking conformations of benzoylaminobenzoic acid derivatives into the active site of FabH enzyme. Mapping the 3D QSAR models into the active site of FabH provides a useful perspective for the active site of FabH.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 5, 1 March 2006, Pages 1474–1482
نویسندگان
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