Meetei Potshangbam Angamba, Rathore R S, Prabhu N Prakash, Vindal Vaibhav
Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, 500046, India.
Bioinformatics Infrastructure Facility, School of Life sciences, University of Hyderabad, Hyderabad, 500046, India.
J Mol Model. 2016 Apr;22(4):71. doi: 10.1007/s00894-016-2945-9. Epub 2016 Mar 11.
Babesiosis is a tick-borne, zoonotic disease caused by species of the intraerythrocytic protozoan Babesia. It is distributed all around the world and affects various domestic and wild animals, mainly cattle. Recently, the cysteine protease enzyme, babesipain-1 from Babesia bigemina has been identified as a potential target for designing new anti-babesiosis drugs. In the present study, a three-dimensional structural model of babesipain-1 was developed. An active site with three pockets (S1, S2, and S3), which is congruent with its homolog, falcipain-3, was also identified. Moreover, the conservation of active site residues was consistent with the cysteine protease family. In order to identify potential inhibitors, a virtual screening workflow was employed with a chemical library containing natural and synthetic compounds. Potential inhibitors interacting with all the three subsites were identified. Further, molecular dynamic simulations were carried out to assess the interactions and stability of the inhibitors. The informatics approach, and the findings presented in this study will assist researchers in further development of potential anti-babesiosis molecules.
巴贝斯虫病是一种由红细胞内原生动物巴贝斯虫属的物种引起的蜱传播人畜共患病。它分布于世界各地，影响各种家畜和野生动物，主要是牛。最近，来自双芽巴贝斯虫的半胱氨酸蛋白酶酶——巴贝斯蛋白酶-1已被确定为设计新型抗巴贝斯虫病药物的潜在靶点。在本研究中，构建了巴贝斯蛋白酶-1的三维结构模型。还确定了一个具有三个口袋（S1、S2和S3）的活性位点，该位点与其同源物恶性疟原虫蛋白酶-3一致。此外，活性位点残基的保守性与半胱氨酸蛋白酶家族一致。为了鉴定潜在的抑制剂，采用了包含天然和合成化合物的化学文库进行虚拟筛选工作流程。鉴定出了与所有三个亚位点相互作用的潜在抑制剂。此外，进行了分子动力学模拟以评估抑制剂的相互作用和稳定性。本研究中提出的信息学方法和研究结果将有助于研究人员进一步开发潜在的抗巴贝斯虫病分子。
