نوع مقاله : مقاله پژوهشی
نویسندگان
1 دانشجوی دکترای بیوفیزیک، دانشکده علوم زیستی، گروه بیوفیزیک، دانشگاه تربیت مدرس، تهران، ایران
2 استاد.بیوفیزیک، علوم زیستی، تربیت مدرس، تهران، ایران
چکیده
تشکیل ساختارهای آمیلوئیدی به دلیل ایجاد بیماری‌هایی مانند آلزایمر، پارکینسون، و دیابت نوع 2، مورد توجه محققان است. از جمله مهارکننده‌های مهم، حلقه‌های ایندولی می‌باشند. مطالعات تجربی بر روی دو نوع ترکیب بیس ایندولی نشان داده است که ترکیب بیس ایندولیل 2-متیل فنیل متان (BI2MPM) مهارکننده‌ی فیبریلاسیون آمیلوئیدی پروتئین لیزوزیم است. اما ترکیب بیس ایندولیل 3-نیترو فنیل متان (BI3NPM) قدرت مهاری چندانیندارد. در این مطالعه با استفاده از روشهای داکینگ و شبیه‌سازی دینامیک مولکولی، میانکنش این دو لیگاند با پروتئین مدل شده‌ی آمیلوئیدی بررسی شد. روش داکینگ مولکولی تمایلی مشابه اما با جایگاه اتصالی متفاوت برای دو لیگاند نشان داد. اما نتایج دینامیک مولکولی نشان داد که لیگاند BI2MPMبا تخریب عمده ساختار بتای هسته های اولیه، موجب کاهش میانکنش بین آن‌ها و با افزایش تغییرات ساختاری در رشته‌های بتا باعث ناپایداری و توقف رشد فیبریلاسیون می‌گردد. اما ترکیب BI3NPM تغییرات اندکی بر ساختار هسته‌های فیبریلی اعمال می‌کند.
کلیدواژه‌ها
عنوان مقاله [English]
Study of Inhibition Potential of Synthetic Bis-Indole Compounds on Amyloid Fibrillation by Molecular Simulation Methods
نویسندگان [English]
- Kaveh Khodayari 1
- Parviz Abdolmaleki. 2
1 Biophysics, Biological Sciences, Tarbiat Modares, Tehran, Iran
2 Professor. Biophysics, Biological Sciences, Tarbiat Modares, Tehran, Iran
چکیده [English]
Aggregation of proteins lead to form amyloid diseases including Alzheimer, Parkinson and diabetes type II has been increasingly considered recently. Compounds including indole rings are the best amyloid aggregation inhibitors. Experimental studies have shown that bis(indolyl)-2-methyl[H1] [M2] phenylmethane (BI2MPM) has a great [H3] [M4] inhibitory potential on Lysozyme amyloid fibril formation, While bis(indolyl)-3-nitrophenylmethane [M5] (BI3NPM) has shown weaker inhibitory power. In this study, the interaction of these two ligands was investigated on amyloid model protein using molecular docking and molecular dynamics simulation techniques. Molecular Docking method showed similar reluctance to both ligands in amyloid nucleus model but in different binding positions. Molecular dynamics simulation showed that BI2MPM with major degradation on the beta structure of early fibril precursors, leads to lower interaction. It also increases structural changes in the subtypes of beta-strands and induces instability and stops fibrillation growth, but BI3NPM has minimum changes on the fibrils core structures
کلیدواژه‌ها [English]
- Amyloid Diseases
- Beta structure
- Indole Ring
- Molecular Dynamics
- Pi interactions
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