According to the world health organization (WHO) reports, Acinetobacter baumannii was considered as one of the significant and first-line priority pathogens, which causes hospital-acquired nosocomial infections in human. The enzymes involved in the peptidoglycan biosynthetic pathway are critical for the survival of this bacterium. Therefore, these enzymes are ideal drug target since they are conserved among most of the species and non-homologous to human. Here, we utilized the structure-based virtual screening (SBVS) technique to identify the promising lead molecules against MurB (UDP-N-acetylenolpyruvoylglucosamine reductase) protein using computational approaches. Initially, the three-dimensional structure of MurB was predicted based on MurB from P. aeruginosa (PDB ID: 4JAY), which is used as a structural template for homology modeling. During the High-throughput Virtual screening (HTVS) analysis, we started with 30,792 molecules against MurB model, among these; only 5238 molecules could be considered suitable for further step. Finally, only twenty molecules were able to pass Lipinski’s and ADMET properties. After a thorough examination of interaction analysis, higher ΔG and Ki values, we had chosen five promising molecules (ZINC IDs: ZINC12530134, ZINC15675540, ZINC15675762, ZINC15675624 and ZINC15707270) and three control molecules (PubChem IDs: 54682555, 729933 and 39964628) for Molecular dynamics (MD) simulation to understand the effect of ligands towards the structural stability, structural integrity and structural compactness of MurB protein. Further, the MM/PBSA binding free energy analysis was performed for eight ligands bound MurB structures. Together the results obtained from global dynamics, essential dynamics and MM-PBSA binding free energy analysis, we concluded that apart from the control molecules, ZINC12530134 should be considered as one of the most promising ones and it could be the potent inhibitor against A baumannii and provide valuable insight for further experimental studies.

根据世界卫生组织（WHO）的报告，鲍曼不动杆菌被认为是重要的一线重要病原体之一，可导致医院获得性医院内人类感染。肽聚糖生物合成途径中涉及的酶对该细菌的存活至关重要。因此，这些酶是理想的药物靶标，因为它们在大多数物种中是保守的并且对人类而言是非同源的。在这里，我们利用基于结构的虚拟筛选（SBVS）技术，通过计算方法确定了针对MurB（UDP-N-乙酰烯醇丙酮酸酰基葡萄糖胺还原酶）蛋白的有前途的铅分子。最初，基于铜绿假单胞菌的MurB预测了MurB的三维结构（PDB ID：4JAY），用作同源性建模的结构模板。在高通量虚拟筛选（HTVS）分析过程中，我们从30,792个针对MurB模型的分子入手，其中包括：仅5238个分子可以被认为适合进一步的步骤。最终，只有二十个分子能够通过Lipinski's和ADMET特性。彻底检查相互作用分析后，较高的ΔG和Ki值，我们选择了五个有前途的分子（ZINC ID：ZINC12530134，ZINC15675540，ZINC15675762，ZINC15675624和ZINC15707270）和三个控制分子（PubChem ID：54682555、729933和39964628）用于分子动力学（MD）模拟，以了解配体对配体的影响MurB蛋白的结构稳定性，结构完整性和结构紧密性。此外，对结合了MurB结构的八个配体进行了MM / PBSA结合自由能分析。结合整体动力学，基本动力学和MM-PBSA结合自由能分析获得的结果，我们得出的结论是，除对照分子外，ZINC12530134应该被认为是最有前途的分子之一，并且可能是针对鲍曼不动杆菌的有效抑制剂。 并为进一步的实验研究提供宝贵的见识。