Sindhu R, Bhat Smitha S, Sangta Jiraporn, Dharmashekar Chandan, Shreevatsa Bhargav, Shivamallu Chandan, Devegowda Devananda, Kollur Shiva Prasad, Ahmad Sheikh F, Attia Sabry M, Sommano Sarana Rose, Prasad Shashanka K
Department of Microbiology, JSS Academy of Higher Education & Research, Mysuru, Karnataka, 570 015, India.
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education & Research, Mysuru, Karnataka, 570 015, India.
Sci Rep. 2024 Dec 2;14(1):29905. doi: 10.1038/s41598-024-81471-2.
Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus, are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a natural food colorant, was examined for its antifungal effects against Aspergillus fumigatus via computational approach against the Ndk protein. Known and predicted interactions of Ndk with proteins was performed using the STRING application. Molecular docking was performed using Schrodinger Maestro software (V.14.1) under enhanced precision docking, with OPLS4 forcefield. MDS was performed for 500ns under OPLS4 forcefield and the TIP3P solvent system. The geometry optimization for DFT was performed using the Becke 3-parameter exchange functional (B3LYP) method. The Molecular Docking Studies revealed significant interactions with good binding energy between Violacein and Ndk. Subsequent MD Simulations confirmed the stability of Violacein-Ndk complex, compared to the reference ligand-complex, indicating a stable interaction between the protein and violacein. The energy band gap of violacein was found to be 0.072567 eV suggesting its softness with lower kinetic stability and higher chemical reactivity. The results suggest Violacein could potentially disrupt nucleotide metabolism by targeting Ndk, thus demonstrating antifungal activity. However, further experimental validation is required to confirm these computational findings and explore the practical use of Violacein in antifungal treatments.
丝状真菌人类病原体（FFHPs），如烟曲霉，对目前可用的抗真菌药物的耐药性正在增强。一个可能的靶点，核苷二磷酸激酶（Ndk），对核苷酸生物合成至关重要，对真菌代谢也至关重要。通过针对Ndk蛋白的计算方法，研究了天然食用色素紫罗碱对烟曲霉的抗真菌作用。使用STRING应用程序进行了Ndk与蛋白质的已知和预测相互作用。使用Schrodinger Maestro软件（V.14.1）在增强精度对接下，采用OPLS4力场进行分子对接。在OPLS4力场和TIP3P溶剂系统下进行了500纳秒的分子动力学模拟（MDS）。使用Becke三参数交换泛函（B3LYP）方法进行密度泛函理论（DFT）的几何优化。分子对接研究揭示了紫罗碱与Ndk之间具有良好结合能的显著相互作用。随后的分子动力学模拟证实了紫罗碱-Ndk复合物与参考配体-复合物相比的稳定性，表明蛋白质与紫罗碱之间存在稳定的相互作用。发现紫罗碱的能带隙为0.072567电子伏特，表明其柔软性、较低的动力学稳定性和较高的化学反应性。结果表明，紫罗碱可能通过靶向Ndk破坏核苷酸代谢，从而显示出抗真菌活性。然而，需要进一步的实验验证来证实这些计算结果，并探索紫罗碱在抗真菌治疗中的实际应用。
