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首页> 外文期刊>Journal of Young Pharmacists >Molecular Docking and Dynamic Simulation Studies of Benzoylated Emodin into HBV Core Protein
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Molecular Docking and Dynamic Simulation Studies of Benzoylated Emodin into HBV Core Protein

机译：苯甲酰大黄素与HBV核心蛋白的分子对接和动力学模拟研究

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Objective: The hepatitis B virus (HBV) core protein was chosen as receptor target for a new, selective and effective due to resistance of current hepatitis B drugs against reverse transcriptase. It forms the capsid of viral particles and essential for viral genome DNA replication and maturation. Emodin was known showing inhibitory effect on HBV replication weakness, but persistent both in vitro and in vivo so still need modification. In this study, emodin derivatives were conducted as an inhibitor candidate of capsid assembly by disruption formation dimer-dimer HBV core protein using molecular docking and dynamic simulation. Methods: Structure-based virtual docking approach was used to design of benzoylated emodin derivatives into HBV core protein as receptor using Molegro Virtual Docker 6.0 program. The stability of interacting residues of proteins with compounds was identified via molecular dynamics and free binding energy calculations using Amber 12. Results: The ligand binding site in an HBV core protein was an interfacial hydrophobic pocket and placed at the dimer-dimer of the core protein interface. Interactions between emodin and derivatives indicated by hydrogen bonding and steric interaction between the ligand with the amino acid residues in the HBV core protein. It is predicted that viral replication would inhibit due to a change in orientation of capsid assembly by core proteins. The benzoylated emodin derivatives showed promising inhibitory profiles better than emodin which were indicated by their binding scores were more negative. Conclusion: This study provides a basis for further chemical design for more effective derivatives of emodin derivatives.
机译：目的：由于当前的乙型肝炎药物对逆转录酶的耐药性，乙型肝炎病毒（HBV）核心蛋白被选作新型，选择性和有效的受体靶标。它形成病毒颗粒的衣壳，对于病毒基因组DNA复制和成熟至关重要。大黄素已知对HBV复制无力具有抑制作用，但在体内和体外均具有持久性，因此仍需要修饰。在这项研究中，大黄素衍生物作为衣壳装配的抑制剂候选物，使用分子对接和动态模拟通过破坏形成二聚体-二聚体的HBV核心蛋白来进行。方法：使用基于结构的虚拟对接方法，使用Molegro Virtual Docker 6.0程序将苯甲酰化大黄素衍生物设计成HBV核心蛋白受体。使用琥珀色12通过分子动力学和自由结合能计算确定了蛋白质与化合物相互作用残基的稳定性。结果：HBV核心蛋白中的配体结合位点是一个界面疏水口袋，位于核心蛋白的二聚体-二聚体上接口。大黄素与衍生物之间的相互作用以氢键和配体与HBV核心蛋白中氨基酸残基之间的空间相互作用表示。据预测，由于核心蛋白衣壳装配的方向改变，病毒复制将受到抑制。苯甲酰大黄素衍生物表现出比大黄素更好的有前途的抑制作用，这是由于它们的结合分数更阴性。结论：该研究为大黄素衍生物的更有效衍生物的进一步化学设计提供了基础。

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