Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mu'tah University, Alkarak Jordan.
Department of Pharmaceutical Chemistry and Pharmacognacy, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan.
Comput Biol Chem. 2018 Jun;74:263-272. doi: 10.1016/j.compbiolchem.2018.03.020. Epub 2018 Mar 19.
Gyrase B is an essential enzyme in the prokaryotes which became an attractive target for antibacterial agents. In our study, we implemented a wide range of docking configurations to dock 120 inhibitors into the in the ATP- binding pocket of Gyrase B enzyme (PDB code: 4GEE). LigandFit docking engines and six scoring functions were utilized in the study. Furthermore, the ligands were docked in their ionized and unionized forms into the hydrous and anhydrous binding pocket. We used docking-based Comparative Intermolecular Contacts Analysis (db-CICA) which is a novel methodology to validate and identify the optimal docking configurations. Three docking configurations were found to achieve self-consistent db-CICA models. The resulting db-CICA models were used to construct corresponding pharmacophoric models that were used to screen the National Cancer Institute (NCI) list of compounds. In-vitro study represents antibacterial activities for twelve hit molecules with the most active having IC of 20.9 μM.
回旋酶 B 是原核生物中一种必不可少的酶，它已成为抗菌药物的一个有吸引力的靶点。在我们的研究中，我们采用了广泛的对接构象，将 120 种抑制剂对接进入回旋酶 B 酶的 ATP 结合口袋（PDB 代码：4GEE）。研究中利用了 LigandFit 对接引擎和六种评分函数。此外，配体以其离子化和非离子化形式对接进入水合和无水结合口袋。我们使用了基于对接的分子间对比接触分析（db-CICA），这是一种新颖的方法来验证和识别最佳对接构象。发现了三种对接构象可以实现自洽的 db-CICA 模型。所得到的 db-CICA 模型被用于构建相应的药效构象模型，该模型用于筛选国家癌症研究所（NCI）的化合物列表。体外研究代表了 12 个命中分子的抗菌活性，其中最活跃的分子的 IC 为 20.9μM。
