Leishmaniasis is a disease caused by protozoan forms called Leishmania which infect animals and humans. The drugs have been in use since half a century due to which there have been mutations in the microbe-facilitating drug resistance. So this provides a reason for searching for effective drugs for the disease. In the current work, an effort has been to find such drugs that act on disease-relevant receptors by similarity indexing method, molecular docking, and dynamics studies. The study focused on the rapid expansion of potential anti-leishmanial compounds that could function as novel natural compound structures for future drug Similarity indexing of existing drugs with natural compounds using Tanimoto clustering resulted in 4 compounds with similarity index of greater than 0.7 (70% similarity). The molecular docking of the resulted compounds was carried out with therapeutic targets CYP51 and GP63 proteins. N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine from Streptomyces griseus showed higher binding affinity in comparison to inhibitor and other selected natural compounds. Simulation studies revealed that the binding configuration of the compound with targets was highly stable all through 10 ns of simulation time with intact hydrogen bonding. The molecular docking and molecular dynamics studies for the selected natural bioactive compound N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine from Streptomyces griseus showed better binding affinity with the selected therapeutics targets and can be further considered for in vitro and in vivo studies which may lead to a possible new drug for the treatment of Leishmaniasis.

中文翻译：

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使用高通量计算增强筛选鉴定靶向利什曼原虫主要CYP51和GP63蛋白的有效天然化合物

利什曼病是由称为利什曼原虫的原生动物形式引起的疾病，感染动物和人类。该药物自半个世纪以来一直在使用，由于微生物促进耐药性发生了突变。因此，这提供了寻找针对该疾病的有效药物的理由。在当前的工作中，人们一直在努力通过相似性索引方法，分子对接和动力学研究来发现对疾病相关受体起作用的药物。该研究集中于潜在的抗利什曼肽化合物的快速扩展，这些化合物可作为未来的新型天然化合物结构使用Tanimoto聚类对现有药物与天然化合物进行相似性索引，结果发现4种化合物的相似性指数均大于0.7（相似性为70％ ）。用治疗靶标CYP51和GP63蛋白对所得化合物进行分子对接。与抑制剂和其他选定的天然化合物相比，来自灰链霉菌的N-甲基酪氨酰-N-甲基酪氨酰-亮氨酰-丙氨酸显示出更高的结合亲和力。模拟研究表明，在完整的氢键作用下，整个10 ns的模拟时间内，化合物与靶标的结合构型都非常稳定。来自灰链霉菌的选定天然生物活性化合物N-甲基酪氨酰-N-甲基酪氨酰-亮氨酰-丙氨酸的分子对接和分子动力学研究显示与选定的治疗靶点具有更好的结合亲和力，可以进一步考虑用于体外和体内研究，导致一种可能用于治疗利什曼病的新药。