Biofuels Institute, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Department of Computer Science, University of Agriculture, Faisalabad 38040, Pakistan.
Department of Computer Science, University of Agriculture, Faisalabad 38040, Pakistan.
Int J Biol Macromol. 2022 Jul 31;213:1088-1097. doi: 10.1016/j.ijbiomac.2022.06.014. Epub 2022 Jun 10.
The vanins are ectoenzymes with pantetheinase activity and are involved in recycling pantothenic acid (vitamin B5) from pantetheine. Elevated levels of vanin have been linked with the development and severity of several diseases, including steatosis, diabetes, skin diseases, cancer, inflammatory diseases etc. Therefore, vanins have previously been used as a potential drug target to combat related diseases. In this study, we used a molecular docking and molecular dynamic simulation-based approach to screen dual inhibitors of hVnn1, and hVnn2 from a library of 120 chemical candidates. Molecular docking of drug candidates with hVnn1, and hVnn2 using GOLD and MOE revealed that the chemical compound "methotrexate (CID: 126941)" has the highest binding affinity against both the target enzymes which was further validated through molecular dynamic simulation. Toxicity profiling of drug candidates evaluated using Lipinski's rule of five and Molsoft tool, and AdmetSar 2.0 confirms the drug suitability of methotrexate, therefore, suggesting its use as a potential therapeutic agent to inhibit the activity of vainin enzyme in related disease conditions.
Vanins 是具有泛酰巯基乙胺水解酶活性的外切酶，参与从泛酰巯基乙胺中回收泛酸（维生素 B5）。Vanin 水平的升高与多种疾病的发展和严重程度有关，包括脂肪变性、糖尿病、皮肤疾病、癌症、炎症性疾病等。因此，vanins 以前曾被用作潜在的药物靶点来治疗相关疾病。在这项研究中，我们使用基于分子对接和分子动力学模拟的方法，从 120 种化学候选物库中筛选 hVnn1 和 hVnn2 的双重抑制剂。使用 GOLD 和 MOE 对候选药物与 hVnn1 和 hVnn2 进行分子对接显示，化学化合物“甲氨蝶呤（CID：126941）”对两种靶酶具有最高的结合亲和力，这通过分子动力学模拟进一步得到了验证。使用 Lipinski 的五规则和 Molsoft 工具以及 AdmetSar 2.0 对候选药物进行毒性分析，确认了甲氨蝶呤的药物适用性，因此，建议将其用作抑制相关疾病中 vainin 酶活性的潜在治疗剂。
