稻瘟病,由真菌稻瘟病引起的,对水稻生产构成严重威胁,特别是在以大米为主食的亚洲。对杀真菌剂抗性和环境影响的担忧引发了对探索天然杀真菌剂作为潜在替代品的兴趣。本研究旨在鉴定针对米曲霉的高效天然杀菌剂,以对抗稻瘟病,使用先进的分子动力学技术。四种关键蛋白(过氧化氢酶过氧化物酶2,混合PKS-NRPS合成酶TAS1,锰脂氧合酶,和PRE-mRNA-拼接因子CEF1)参与米曲霉感染过程。编制了30种具有记录的抗真菌特性的植物代谢物的清单,以评估为潜在的杀真菌剂。分子对接研究表明,2-香豆酰基奎尼酸,杨梅素,迷迭香酸,与参考杀真菌剂(唑酯和三环唑)相比,槲皮素和槲皮素表现出优异的结合亲和力。进行了高通量分子动力学模拟,分析像RMSD这样的参数,RMSF,Rg,SASA,氢键,接触分析,吉布斯自由能,和聚类分析。结果揭示了所选代谢物与靶蛋白之间的稳定相互作用,涉及重要的氢键和接触。SwissADME服务器分析表明,代谢物具有杀真菌特性,使它们成为有效和安全的杀菌剂,对环境和生物毒性低。此外,生物活性测定证实了它们作为核受体配体和酶抑制剂的生物活性。总的来说,这项研究为防治稻瘟病的潜在天然杀菌剂提供了有价值的见解,与2-香马酰基奎尼酸,杨梅素,迷迭香酸,槲皮素是传统杀菌剂的有前途和环保的替代品。这些发现对制定作物保护战略和加强全球粮食安全具有重要意义。特别是在依赖水稻的地区。
Rice blast disease, caused by the fungus
Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae\'s infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.