Molecular Modelling Research Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telagana, India.
Department of Chemistry, Nizam College, Osmania University, Hyderabad, Telangana, India.
J Cell Biochem. 2023 Jun;124(6):836-848. doi: 10.1002/jcb.30412. Epub 2023 May 9.
Phosphatidyl-myo-inositol mannosyltransferase (Pim) is a subset of the Glycosyl transferase type family that has been synthesized from 1D-myo-inositol and GDP-α-d-mannose reaction in the presence of PimA protein as a catalyst, which PimA protein is identified as a high-confidence therapeutic target. In-silico technique such as homology modeling is the most efficient approach for discovering a new framework to study the modulations of protein function. Using In-silico approaches, therapeutic compounds with high affinity, specificity, activity, low harmfulness, and no side effects can be found. Applying the Modeller software and molecular dynamics simulations, a stable three-dimensional (3D) model of the PimA protein is produced. The modeled PimA protein consists of 20 helices and 27 twists in its 3D structure. Lead compounds that inhibit the PimA protein are found by applying the Schrodinger suite and the PyRx virtual screening tools. The amino acid residues PRO14 and ASP253 are identified as active residues involved in binding with the ligands. High-potential lead compounds are discovered as ligand scaffolds against PimA protein with satisfactory ADME capabilities.
磷酸肌醇甘露糖基转移酶（Pim）是糖基转移酶家族的一个亚类，它是在 PimA 蛋白作为催化剂的存在下，由 1D-肌醇和 GDP-α-d-甘露糖反应合成的，PimA 蛋白被确定为高可信度的治疗靶点。同源建模等计算机技术是发现研究蛋白质功能调节的新框架的最有效方法。通过使用计算机技术，可以找到具有高亲和力、特异性、活性、低毒性和无副作用的治疗化合物。应用 Modeller 软件和分子动力学模拟，产生了 PimA 蛋白的稳定三维（3D）模型。模型化的 PimA 蛋白在其 3D 结构中由 20 个螺旋和 27 个扭曲组成。通过应用 Schrodinger 套件和 PyRx 虚拟筛选工具，找到了抑制 PimA 蛋白的先导化合物。鉴定出 PRO14 和 ASP253 氨基酸残基为与配体结合的活性残基。发现具有满意的 ADME 能力的高潜力先导化合物作为针对 PimA 蛋白的配体支架。
