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Abstract：
The present study was focused on exploring the efficient inhibitors of closed state (form) of type III effector Xanthomonas outer protein Q (XopQ) (PDB: 4P5F) from the 44 phytochemicals of Picrasma quassioides using cutting-edge computational analysis. Among them, Kumudine B showed excellent binding energy (-11.0 kcal/mol), followed by Picrasamide A, Quassidine I and Quassidine J with the targeted closed state of XopQ protein compared to the reference standard drug (Streptomycin). The molecular dynamics (MD) simulations performed at 300 ns validated the stability of top lead ligands (Kumudine B, Picrasamide A, and Quassidine I)-bound XopQ protein complex with slightly lower fluctuation than Streptomycin. The MM-PBSA calculation confirmed the strong interactions of top lead ligands (Kumudine B and QuassidineI) with XopQ protein, as they offered the least binding energy. The results of absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed that Quassidine I, Kumudine B and Picrasamide A were found to qualify most of the drug-likeness rules with excellent bioavailability scores compared to Streptomycin. Results of the computational studies suggested that Kumudine B, Picrasamide A, and Quassidine I could be considered potential compounds to design novel antibacterial drugs against X. oryzae infection. Further in vitro and in vivo antibacterial activities of Kumudine B, Picrasamide A, and Quassidine I are required to confirm their therapeutic potentiality in controlling the X. oryzae infection.
摘要：
本研究的重点是使用尖端的计算分析，从Picrasmaquassioides的44种植物化学物质中探索III型效应黄单胞菌外部蛋白Q（XopQ）（PDB：4P5F）的封闭状态（形式）的有效抑制剂。其中,KumudineB表现出优异的结合能（-11.0kcal/mol），其次是苦果胺A,与参考标准药物（链霉素）相比，QuassidineI和QuassidineJ具有XopQ蛋白的靶向封闭状态。在300ns下进行的分子动力学（MD）模拟验证了顶部铅配体（KummudineB，苦果胺A,和QuassidineI）结合的XopQ蛋白复合物，波动略低于链霉素。MM-PBSA计算证实了顶部铅配体（KumudineB和QuasidineI）与XopQ蛋白的强相互作用，因为它们提供了最小的结合能。吸收的结果，分布，新陈代谢，排泄,和毒性(ADMET)分析证实QuasidineI，与链霉素相比，发现KumudineB和PicrasamideA符合大多数药物相似度规则，具有出色的生物利用度评分。计算研究的结果表明，KumudineB，苦果胺A,和QuassidineI可以被认为是设计针对X的新型抗菌药物的潜在化合物。米zae感染。KumudineB的进一步体内外抗菌活性，苦果胺A,和QuassidineI需要确认其在控制X.米zae感染方面的治疗潜力。
