کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4953233 1442946 2017 31 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Assessing the binding of cholinesterase inhibitors by docking and molecular dynamics studies
ترجمه فارسی عنوان
ارزیابی اتصال مهار کننده های کولین استراز به وسیله مطالعات تکاملی و دینامیک مولکولی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
چکیده انگلیسی
In this report we assessed by docking and molecular dynamics the binding mechanisms of three FDA-approved Alzheimer drugs, inhibitors of the enzyme acetylcholinesterase (AChE): donepezil, galantamine and rivastigmine. Dockings by the softwares Autodock-Vina, PatchDock and Plant reproduced the docked conformations of the inhibitor-enzyme complexes within 2 Å of RMSD of the X-ray structure. Free-energy scores show strong affinity of the inhibitors for the enzyme binding pocket. Three independent Molecular Dynamics simulation runs indicated general stability of donepezil, galantamine and rivastigmine in their respective enzyme binding pocket (also referred to as gorge) as well as the tendency to form hydrogen bonds with the water molecules. The binding of rivastigmine in the Torpedo California AChE binding pocket is interesting as it eventually undergoes carbamylation and breaks apart according to the X-ray structure of the complex. Similarity search in the ZINC database and targeted docking on the gorge region of the AChE enzyme gave new putative inhibitor molecules with high predicted binding affinity, suitable for potential biophysical and biological assessments.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 76, September 2017, Pages 36-42
نویسندگان
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