目的:本研究旨在通过研究特定草药化合物与牙龈卟啉单胞菌血红素结合蛋白之间的分子相互作用,探索草药对慢性牙周炎的治疗潜力。与疾病有关的关键病原体。
方法:从蛋白质数据库获得血红素结合蛋白的晶体结构。通过广泛的文献综述鉴定了草药化合物。进行分子对接模拟以预测结合亲和力,其次是吸收,Distribution,代谢,和排泄(ADME)参数预测。药物相似性是根据利平斯基的“五”法则进行评估的,进行药效团建模以确定关键的分子相互作用。
结果:分子对接模拟显示,鱼藤酮,和杨梅素表现出显著的结合亲和力血红素结合蛋白,对接评分为-6.5kcal/mol,-6.4千卡/摩尔,和-6.1千卡/摩尔,分别。这些化合物与结合袋内的关键氨基酸残基形成稳定的相互作用。ADME分析表明,所有3个化合物具有良好的药代动力学性质,没有违反Lipinski的规则和最小的预测毒性。药效团建模进一步阐明了相互作用谱,突出特定的氢键和疏水相互作用的关键结合效力。
结论:切尔西多宁,鱼藤酮,和杨梅素由于其强大的结合亲和力而成为慢性牙周炎的有希望的治疗候选药物,有利的ADME配置文件,缺乏明显的毒性。详细的药效基团建模提供了对支撑其对牙龈卟啉单胞菌血红素结合蛋白抑制作用的分子机制的见解。这些发现表明,这些化合物具有进一步开发作为慢性牙周炎有效治疗方法的潜力。未来的研究应集中在这些发现的体外和体内验证,以确认这些化合物在生物系统中的功效和安全性。
OBJECTIVE: This study aimed to explore the therapeutic potential of medicinal herbs for chronic periodontitis by examining the molecular interactions between specific herbal compounds and the heme-binding protein of Porphyromonas gingivalis, a key pathogen involved in the disease.
METHODS: The crystal structure of heme-binding protein was obtained from the Protein Data Bank. Herbal compounds were identified through an extensive literature review. Molecular docking simulations were performed to predict binding affinities, followed by Absorption, Distribution, Metabolism, and Excretion (ADME) parameter prediction. Drug-likeness was assessed based on Lipinski\'s Rule of Five, and pharmacophore modeling was conducted to identify key molecular interactions.
RESULTS: The molecular docking simulations revealed that chelidonine, rotenone, and myricetin exhibited significant binding affinities to the heme-binding protein, with docking scores of -6.5 kcal/mol, -6.4 kcal/mol, and -6.1 kcal/mol, respectively. These compounds formed stable interactions with key amino acid residues within the binding pocket. ADME analysis indicated that all 3 compounds had favourable pharmacokinetic properties, with no violations of Lipinski\'s rules and minimal predicted toxicity. Pharmacophore modeling further elucidated the interaction profiles, highlighting specific hydrogen bonds and hydrophobic interactions critical for binding efficacy.
CONCLUSIONS: Chelidonine, rotenone, and myricetin emerged as promising therapeutic candidates for chronic periodontitis due to their strong binding affinities, favorable ADME profiles, and lack of significant toxicity. The detailed pharmacophore modeling provided insights into the molecular mechanisms underpinning their inhibitory effects on the heme-binding protein of P. gingivalis. These findings suggest that these compounds have the potential for further development as effective treatments for chronic periodontitis. Future research should focus on in vitro and in vivo validation of these findings to confirm the efficacy and safety of these compounds in biological systems.