Shaikh Ibrahim Ahmed, Muddapur Uday M, C Krithika, Badiger Shrikanth, Kulkarni Madhura, Mahnashi Mater H, Alshamrani Saleh A, Huneif Mohammed A, More Sunil S, Khan Aejaz Abdullatif, Iqubal S M Shakeel
Department of Pharmacology, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia.
Department of Biotechnology, KLE Technological University, BVB Campus, Hubballi 580031, Karnataka, India.
Molecules. 2022 Feb 23;27(5):1513. doi: 10.3390/molecules27051513.
Current drug discovery involves finding leading drug candidates for further development. New scientific approaches include molecular docking, ADMET studies, and molecular dynamic simulation to determine targets and lead compounds. Hepatitis B is a disease of concern that is a life-threatening liver infection. The protein considered for the study was HBx. The hepatitis B X-interacting protein crystal structure was obtained from the PDB database (PDB ID-3MSH). Twenty ligands were chosen from the PubChem database for further in silico studies. The present study focused on in silico molecular docking studies using iGEMDOCK. The triethylene glycol monoethyl ether derivative showed an optimum binding affinity with the molecular target HBx, with a high negative affinity binding energy of -59.02 kcal/mol. Lipinski's rule of five, Veber, and Ghose were followed in subsequent ADMET studies. Molecular dynamic simulation was performed to confirm the docking studies and to analyze the stability of the structure. In these respects, the triethylene glycol monoethyl ether derivative may be a promising molecule to prepare future hepatitis B drug candidates. Substantial research effort to find a promising drug for hepatitis B is warranted in the future.
当前的药物研发涉及寻找有潜力的药物候选物以进行进一步开发。新的科学方法包括分子对接、ADMET研究和分子动力学模拟，以确定靶点和先导化合物。乙型肝炎是一种令人关注的疾病，是一种危及生命的肝脏感染。本研究考虑的蛋白质是HBx。乙型肝炎X相互作用蛋白晶体结构是从PDB数据库（PDB ID - 3MSH）获得的。从PubChem数据库中选择了20种配体用于进一步的计算机模拟研究。本研究重点是使用iGEMDOCK进行计算机模拟分子对接研究。三甘醇单乙醚衍生物与分子靶点HBx表现出最佳结合亲和力，结合能为 - 59.02 kcal/mol，具有较高的负亲和力。后续的ADMET研究遵循了Lipinski的五规则、Veber规则和Ghose规则。进行分子动力学模拟以确认对接研究并分析结构的稳定性。在这些方面，三甘醇单乙醚衍生物可能是制备未来乙型肝炎药物候选物的有前景的分子。未来有必要投入大量研究精力来寻找一种有前景的乙型肝炎药物。
