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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Elucidation the binding mechanism of Nelumbo nucifera-derived isoquinoline alkaloids as Rho-kinase 1 inhibitors by molecular docking and dynamic simulation
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Elucidation the binding mechanism of Nelumbo nucifera-derived isoquinoline alkaloids as Rho-kinase 1 inhibitors by molecular docking and dynamic simulation

机译：通过分子对接和动态模拟阐明Nelumbo Nucifera衍生的异喹啉生物碱作为Rho-kinase1抑制剂的结合机理

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摘要

Rho-kinase 1 (ROCK1) is a key molecular target for controlling smooth muscle (SM) contraction in asthma, gastrointestinal disorders, hypertension. Embryos of lotus seed (Nelumbo nucifera) are traditional folk herbs widely used in treating various diseases which are closely related to SM contraction. With the aim of explaining the mechanism of embryos of lotus seed, 27 isoquinoline alkaloids were isolated from the embryos of lotus seed, the inhibitory activity of these alkaloids against ROCK1 were virtual screened via molecular docking and molecular dynamics (MD) simulations. The docking results indicated that 5 bisbenzylisoquinolines (BBIs) and 1 tribenzylisoquinoline (TBI) were potent inhibitors with high binding affinity for both A and B chains of ROCK1 (AcRock and BcRock). The MD results also revealed that neoliensinine (28) was the most potent inhibitor, which was corresponding to the irreversible relaxation effect of neoliensinine on SM. Moreover, through the MD simulation, it also indicated that neoliensinine (28) interacted in its stretched conformation through polar solvation interactions and van der Waal forces. Finally, with the best calculation results, the inhibition effect of neoliensinine (28) on the contraction of vascular smooth muscle cells (VSMCs) and ROCK1 was also confirmed by several biological tests. Communicated by Ramaswamy H. Sarma
机译：Rho激酶1（ROCK1）是控制哮喘、胃肠道疾病、高血压患者平滑肌收缩的关键分子靶点。莲子胚（Nelumbo nucifera）是民间传统草药，广泛用于治疗与SM收缩密切相关的各种疾病。为了解释莲子胚的形成机制，从莲子胚中分离出27种异喹啉生物碱，通过分子对接和分子动力学（MD）模拟虚拟筛选这些生物碱对ROCK1的抑制活性。对接结果表明，5个双苄基异喹啉（BBI）和1个三苄基异喹啉（TBI）是对ROCK1（AcRock和BcRock）的A链和B链具有高结合亲和力的有效抑制剂。MD结果还表明，新连烯辛烷（28）是最有效的抑制剂，这与新连烯辛烷对SM的不可逆松弛作用相对应。此外，通过MD模拟，它还表明新连烯辛碱（28）在其拉伸构象中通过极性溶剂化作用和范德华力相互作用。最后，在最佳计算结果的情况下，新烯雌酚碱（28）对血管平滑肌细胞（VSMC）和ROCK1收缩的抑制作用也通过若干生物学试验得到证实。由Ramaswamy H.Sarma传达

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