title

شاخص های کارآیی باندینگ در طراحی مولکول های زیست فعال: یک روش محاسباتی در جهت طراحی مهارکننده های آنزیم بتا-سکرتاز

رزاقی اصل, نیما and میری, رامین and عبادی, احمد and ادراکی, نجمه and شهابی پور, سارا (1392) شاخص های کارآیی باندینگ در طراحی مولکول های زیست فعال: یک روش محاسباتی در جهت طراحی مهارکننده های آنزیم بتا-سکرتاز. Iranian Journal of Pharmaceutical Research ــ 12 (3). pp. 423-436. شاپا 1735-0328

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Title

Fragment-based Binding Efficiency Indices in Bioactive Molecular Design: A Computational Approach to BACE-1 Inhibitors

English Abstract

One of the most important targets in Alzheimer disease is Beta site amyloid precursor protein cleaving enzyme-1 (BACE-1). It is a membrane associated protein and is one of the main enzymes responsible for amyloid β (Aβ) production. Up to now, a considerable number of peptidic and non-peptidic inhibitors of BACE-1 have been developed. Recently, small molecule BACE-1 inhibitors have attracted the attention of scientists, because peptidic inhibitors have many pharmacokinetic problems. In the present study, several small molecule BACE-1 inhibitors were extracted from Brookhaven Protein Databank (PDB) and subjected to dissection analysis to achieve constructing fragments. Atom type, hybridization, and bond order were considered for generated constitutional fragments (simplified structures). AutoDock version 4.2 was applied to dock various chemical fragments into BACE-1 active site. The benefits of such studies have been well revealed in previous reports. On the basis of obtained binding affinities, fragment-based ligand efficiency (LE) indices were estimated. These theoretical binding efficiencies were applied to further elucidate the key structural features of BACE-1 inhibitors. Typical results of the study were elucidated and we suggested the ways these findings might be beneficial to guide rational bioactive molecular developments. Our study confirmed that the evaluation of ligand-receptor interactions in terms of ligand efficiency indices (binding energy per atom and pKi per MW) could be a helpful strategy in structure-based drug discovery (SBDD) strategies.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نیما رزاقی اصل
نویسنده مسئول :رامین میری
نویسنده :احمد عبادی
نویسنده :نجمه ادراکی
نویسنده :سارا شهابی پور
Additional Information:Impact Factor (2013): 0.510 Indexing Databases , Science Citation Index Expanded , Embase , Scopus , BIOSIS Previews , DOAJ (Directory of Open Access Journals) , Index Copernicus
Uncontrolled Keywords:آلزایمر، آنزیم بتا-سکرتاز، داکینگ، کارآیی لیگاند
کلیدواژه ها (انگلیسی):Alzheimer; BACE-1; Docking; Ligand efficiency
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:6072
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:26 Aug 1393 05:26
Last Modified:26 Aug 1393 05:26

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