Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
Department of Environmental Science and Management School of Environment and Life Sciences, Independent University Bangladesh, Dhaka, Bangladesh.
J Biomol Struct Dyn. 2022 Jul;40(10):4475-4487. doi: 10.1080/07391102.2020.1859411. Epub 2020 Dec 15.
A metabolic network of energy-sensing molecular pathways drives the biological ageing process. Regulating certain network elements can help decelerate the ageing process and ameliorate ageing associated disorders. Bioactive phytopeptides are a prospective avenue for anti-ageing therapeutics and rejuvenation biotechnology. The present study investigates the potential of therapeutic plant peptides against cellular senescence by targeting three key proteins in the ageing network - target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). This investigation screened a library of reported bioactive peptides using standard cheminformatic methods including ADMET, molecular docking, molecular dynamics simulation and molecular mechanics calculation. The retrieved simulation data predict 25 diverse phytopeptides as potential safe and drug-like anti-ageing biologics with half-lives >20 h and bioavailability scores >0.40. The best docked peptide, Cycloleonuripeptide B, exhibited strong binding affinity and stable complex formation with mTOR (-17.5 kCal/mol), SIRT1 (-28.54 kCal/mol) and two active sites in AMPK (-41.8 kCal/mol; -36.0 kCal/mol) during molecular dynamics simulations. The computational study acts as a foundation for future laboratory and clinical research into the potential of repurposing therapeutic phytopeptides against cellular senescence and associated pathophysiology. Communicated by Ramaswamy H. Sarma.
能量感应分子通路代谢网络驱动着生物衰老过程。调节某些网络元素有助于减缓衰老过程并改善与衰老相关的疾病。生物活性植物肽是抗衰老治疗和恢复生物技术的有前途的途径。本研究通过靶向衰老网络中的三种关键蛋白——雷帕霉素靶蛋白 (mTOR)、单磷酸腺苷激活蛋白激酶 (AMPK) 和 SIRT1——研究了治疗植物肽对细胞衰老的潜在作用。该研究使用标准计算化学方法筛选了报告的生物活性肽文库，包括 ADMET、分子对接、分子动力学模拟和分子力学计算。检索到的模拟数据预测 25 种不同的植物肽可能是安全且具有药物样特性的抗衰老生物制剂，半衰期>20 小时，生物利用度评分>0.40。最佳对接肽 Cycloleonuripeptide B 在分子动力学模拟中与 mTOR（-17.5 kCal/mol）、SIRT1（-28.54 kCal/mol）和 AMPK 的两个活性位点（-41.8 kCal/mol；-36.0 kCal/mol）表现出强烈的结合亲和力和稳定的复合物形成。这项计算研究为未来实验室和临床研究提供了基础，以研究重新利用治疗性植物肽对抗细胞衰老和相关病理生理学的潜力。由 Ramaswamy H. Sarma 传达。
