Dhanjal Jaspreet Kaur, Grover Sonam, Paruthi Prateek, Sharma Sudhanshu, Grover Abhinav
School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.
Comb Chem High Throughput Screen. 2014 Feb;17(2):124-31. doi: 10.2174/13862073113166660061.
Insomnia is one of the most common clinical problems being faced by people all over the world. It adversely affects the routine life of these patients giving rise to even other health issues like hypertension, diabetes, obesity, depression, heart attack, and stroke. Orexin receptor-1 (OX1R), a noteworthy drug target, when inhibited can promote sleepiness in people suffering from such conditions. OX1R is a G-protein coupled receptor which is conserved throughout the mammalian species and is located primarily in hypothalamus and locus coeruleus. The present study aims at identifying potent natural-origin inhibitors of OX1R capable of affecting the arousal and sleep pattern. In the present work, we have screened a large dataset of natural compounds against OX1R using high throughput screening and high precision docking approaches. Molecular dynamics simulations were carried out to study the dynamical behavior of the top scoring compound. We also provided mechanistic insights into the binding mode of action of this compound. The study provides evidence for consideration of this natural molecule as prospective lead in treatment of insomnia.
失眠是全世界人们面临的最常见临床问题之一。它对这些患者的日常生活产生不利影响，甚至引发其他健康问题，如高血压、糖尿病、肥胖症、抑郁症、心脏病发作和中风。食欲素受体-1（OX1R）是一个值得关注的药物靶点，受到抑制时可促进患有此类病症的人的嗜睡。OX1R是一种G蛋白偶联受体，在整个哺乳动物物种中保守，主要位于下丘脑和蓝斑。本研究旨在鉴定能够影响觉醒和睡眠模式的强效天然来源的OX1R抑制剂。在目前的工作中，我们使用高通量筛选和高精度对接方法针对OX1R筛选了大量天然化合物数据集。进行了分子动力学模拟以研究得分最高的化合物的动力学行为。我们还对该化合物的结合作用模式提供了机制见解。该研究为将这种天然分子视为治疗失眠的潜在先导物提供了证据。
