Computational design of a chimeric toxin against Claudin-۴-expressing cancer cells: molecular modeling, docking and molecular dynamics simulation analysis
محل انتشار: گفتمان پژوهش دامپزشکی، دوره: 14، شماره: 5
سال انتشار: 1402
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 66
فایل این مقاله در 7 صفحه با فرمت PDF قابل دریافت می باشد
- صدور گواهی نمایه سازی
- من نویسنده این مقاله هستم
استخراج به نرم افزارهای پژوهشی:
شناسه ملی سند علمی:
JR_VRFAN-14-5_003
تاریخ نمایه سازی: 25 آبان 1402
چکیده مقاله:
Cancer is one of the main reasons of mortality all over the world. Over the time, the major ways for cancer-therapy were based on radiotherapy, chemotherapy and surgery. These methods are not specific enough for that purpose, therefore, new ideas for design of new drugs with higher specificity are considered. Chimeric protein toxins are hybrid proteins consisting of a targeting portion and a toxic one which specifically bind and kill the target cancer cells. The main purpose of this study was designing a recombinant chimeric toxin with biding capability to one of the most key receptors namely claudin-۴ which is over-expressed in almost all cancer cells. To design it, we utilized the last ۳۰ C-terminal amino acids of Clostridium perfringens enterotoxin (CPE) as a binding module for claudin-۴ and the toxic module which is the A-domain of Shiga toxin from Shigella dysenteriae. Using molecular modeling and docking methods, appropriate binding affinity of the recombinant chimeric toxin to its specific receptor was demonstrated. In the next step, the stability of this interaction was investigated by molecular dynamics simulation. Although partial instability was detected at some time points, however, sufficient stable situation of hydrogens bonds and high binding affinity between the chimeric toxin and receptor were observed in the in silico studies which in turn suggested that this complex could be formed successfully.
کلیدواژه ها:
نویسندگان
Sepehr Safaei
Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Mehdi Imani
Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
مراجع و منابع این مقاله:
لیست زیر مراجع و منابع استفاده شده در این مقاله را نمایش می دهد. این مراجع به صورت کاملا ماشینی و بر اساس هوش مصنوعی استخراج شده اند و لذا ممکن است دارای اشکالاتی باشند که به مرور زمان دقت استخراج این محتوا افزایش می یابد. مراجعی که مقالات مربوط به آنها در سیویلیکا نمایه شده و پیدا شده اند، به خود مقاله لینک شده اند :