School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India.
School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India.
Bioorg Med Chem. 2019 Jun 15;27(12):2553-2571. doi: 10.1016/j.bmc.2019.03.039. Epub 2019 Mar 22.
Plasmodium vivax (Pv) is the second most malaria causing pathogen among Plasmodium species. M18 aspartic aminopeptidase (M18AAP) protein is a single gene copy present in Plasmodium. This protein is functional at the terminal stage of hemoglobin degradation of host and completes the hydrolysis process which makes it an important target for new chemotherapeutics. No experimental and structural study on M18AAP protein of P. vivax is reported till today. This paper advocates the application of multiple computational approaches like protein model prediction, ligand-based 3D QSAR study, pharmacophore, structure-based virtual screening and molecular docking simulation for identification of potent lead molecules against the enzyme. The 3D QSAR model was developed using known bioactive compounds against the PvM18AAP protein which statistically signify the k-NN model with q^2 = 0.7654. The study reports a lead molecule from ligand-centric approach with good binding affinity and possessing lowest docking score. The findings will be helpful for in-vivo and in-vitro validations and development of potent anti-malarial molecules against the drug resistant strains of malaria parasite.
疟原虫 vivax(Pv)是疟原虫属中第二大可引起疟疾的病原体。M18 天冬氨酸氨肽酶(M18AAP)蛋白是存在于疟原虫中的单个基因副本。该蛋白在宿主血红蛋白降解的终末阶段发挥功能,完成水解过程,因此成为新化学疗法的重要靶标。迄今为止,尚未有关于疟原虫 vivax 的 M18AAP 蛋白的实验和结构研究报告。本文主张应用多种计算方法,如蛋白质模型预测、基于配体的 3D-QSAR 研究、药效团、基于结构的虚拟筛选和分子对接模拟,以鉴定针对该酶的有效先导分子。该 3D-QSAR 模型是使用针对 PvM18AAP 蛋白的已知生物活性化合物开发的,该模型在统计学上表示 k-NN 模型,q^2 = 0.7654。该研究报告了一种来自配体中心方法的先导分子,具有良好的结合亲和力和最低的对接评分。这些发现将有助于针对抗药性疟原虫株进行体内和体外验证以及开发有效的抗疟药物。