ABSTRACT Inhibitors of monoamine oxidase (MAO)-B have been used for many years in the therapy of Parkinson’s disease (PD). Owing to the safety concerns of the currently used agents, the discovery of novel scaffolds is of considerable interest. MAO-B inhibitory potential of rutin, a flavonoid derived from natural sources, has been established in experimental findings. Hence, the current study seeks to examine the interactions between rutin and crystal structure of human MAO-B enzyme. Molecular docking calculations, as well as molecular dynamics simulations, were employed to investigate the binding mode and the stability of the rutin/MAO-B complex. Energies of highest occupied/lowest unoccupied molecular orbitals were computed through DFT studies and used to calculate electron affinity, hardness, chemical potential, electronegativity, and electrophilicity index in order to investigate the capability of these parameters to influence the ligand–receptor interactions. It was found that rutin traverses both the entrance cavity and the substrate cavity, forcing the Ile-199 ‘gate’ to rotate into its open conformation. It results in the fusion of the two cavities of the MAO-B binding site and directly leads to better binding interactions. Results of the current study can be used for lead modification and development of novel drugs for the treatment of PD.

中文翻译：

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芦丁作为治疗帕金森病的有前途的药物：通过对接、分子动力学和 DFT 研究评估 MAO-B 抑制潜力

摘要 单胺氧化酶 (MAO)-B 抑制剂已用于治疗帕金森病 (PD) 多年。由于目前使用的药剂的安全性问题，新型支架的发现引起了相当大的兴趣。芦丁是一种天然来源的黄酮类化合物，其 MAO-B 抑制潜力已在实验结果中得到证实。因此，目前的研究旨在检查芦丁与人 MAO-B 酶晶体结构之间的相互作用。采用分子对接计算以及分子动力学模拟来研究芦丁/MAO-B 复合物的结合模式和稳定性。通过 DFT 研究计算最高占据/最低未占据分子轨道的能量，并用于计算电子亲和力、硬度、化学势、电负性、和亲电指数，以研究这些参数影响配体-受体相互作用的能力。发现芦丁穿过入口腔和基底腔，迫使 Ile-199“门”旋转到其开放构象。它导致 MAO-B 结合位点的两个空腔的融合，并直接导致更好的结合相互作用。目前的研究结果可用于先导修饰和开发治疗 PD 的新药物。它导致 MAO-B 结合位点的两个空腔的融合，并直接导致更好的结合相互作用。目前的研究结果可用于先导修饰和开发治疗 PD 的新药物。它导致 MAO-B 结合位点的两个空腔的融合，并直接导致更好的结合相互作用。目前的研究结果可用于先导修饰和开发治疗 PD 的新药物。