چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده ثبت کننده مقاله | محمد مصطفی پورسیف |
| مرحله جاری مقاله | تایید نهایی |
| دانشکده/مرکز مربوطه | مرکز تحقیقات ریز فناوری دارویی |
| کد مقاله | 84554 |
| عنوان فارسی مقاله | طراحی روشهای درمانی مبتنی بر PROTAC بر علیه پروتئینهای جهش یافته p53 از طریق غربالگری مجازی ساختار محور و شبیه سازی داینامیک |
| عنوان لاتین مقاله | Designing targeted PROTAC-based therapeutics against mutant p53 proteins through structure-based virtual screening and dynamic simulations |
| نوع ارائه | پوستر |
| عنوان کنگره / همایش | سومین همایش بین المللی و دوازدهمین همایش ملی بیوانفورماتیک ایران |
| نوع کنگره / همایش | بین المللی |
| کشور محل برگزاری کنگره/ همایش | Iran (Islamic Republic) |
| شهر محل برگزاری کنگره/ همایش | بهشهر |
| سال انتشار/ ارائه شمسی | 1402 |
| سال انتشار/ارائه میلادی | 2024 |
| تاریخ شمسی شروع و خاتمه کنگره/همایش | 1402/12/09 الی 1402/12/10 |
| آدرس لینک مقاله/ همایش در شبکه اینترنت | https://icb12.ibis.org.ir/ |
| آدرس علمی (Affiliation) نویسنده متقاضی | Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran |
| نویسنده | نفر چندم مقاله |
|---|---|
| احسان مفیدی چلان | اول |
| محمد مصطفی پورسیف | پنجم |
| امیر ضارب کهن | دوم |
| رضا حسنی | سوم |
| آیلار نخلبند | چهارم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | More than half of cancers bear TP53 mutations, that drive tumorigenesis and progression through having gain-of-function effects [1]. Despite p53 variants are considered as 'undruggable' targets, efforts have been made in p53-targeted therapies, but challenges remain in clinical development. Proteolysis-targeting chimeras (PROTACs) are a rapidly evolving technology which target undruggable proteins through inducing their degradation. PROTACs are heterobifunctional molecules that consist of a ligand for the target protein, a ligand for the E3 ubiquitin ligase, and a linker connecting the two ends [2]. Herein, we used structure-based virtual screening and dynamic simulations to design a PROTAC system that targets a specific mutated form of the p53 protein known as p53(Y220C). By using molecular docking technology, we virtually screened a large number of peptides to identify those that have a high affinity for the target protein. This screening process involves predicting the binding interactions (and energies) between the peptides and the target protein based on their structural compatibility. To build our PROTAC system, we used previously used E3 ubiquitin ligase binder and linkers with our candidate peptide. The final construct evaluated for its stability efficacy and safety through 100ns molecular dynamics (MD) simulations and based on GROMOS96 54a7 force field for understanding atomic level motion and interactions of the PROTAC-based designed peptide in complex with TP53. The analyses of RMSD (Root Mean Square Deviation), RMSF (Root Mean Square Fluctuation), radius of gyration, and hydrogen bond formation indicate that the designed lead PROTACs exhibit stable interactions throughout the simulation period. The subsequent breakdown of the p53(Y220C) mutant via the PROTAC system may aid in restoring or stabilizing the typical structure of the p53 protein, thereby presenting a potentially innovative therapeutic approach for combating cancer. However, further in vitro and in vivo studies needed to ensure its effectiveness and safety. |
| کلمات کلیدی | Cancer; Molecular dynamic simulation; PROTAC; TP53; Virtual screening |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| Certificate511002 (2).pdf | 1403/02/05 | 307743 | دانلود |
| Certificate511002.pdf | 1403/02/05 | 412560 | دانلود |
| BookletFinalFileFinal.pdf | 1403/03/05 | 12696106 | دانلود |
