Beta-lactamase (ampC) in general causes the onset of antibiotic resistance in pathogenic bacteria against the β-lactam antibiotics. Morganella morganii which belongs to the Proteae tribe of the Enterobacteriaceae family is a Gram-negative bacillus. Gram-negative bacteria are the key problematic agents among the human population in overexpressing resistance against β-lactam antibiotics. These β-lactam antibiotics being experimentally well studied still lack the key information and mechanism for their resistance. The structural information of the ampC protein is unknown and poorly studied; hence, it is the need of the hour to find effective inhibitors against it. In our study, the prediction of the three-dimensional structure of ampC protein from Morganella morganii was performed using a comparative modelling approach. The predicted structure was energetically stabilized and functional conformations were mapped through 100-ns molecular dynamics simulation runs. Also, Ramachandran plot shows the model to be stereo-chemically stable with most residues found under core allowed regions. Drug screening with several experimentally tested inhibitors was then confirmed to check the activity against ampC protein using an AutoDock tool. The results suggested OncoglabrinolC molecule as the best inhibitor (out of 21 drug molecules) with a binding affinity of − 11.44 kcal/mol. Anti-bacterial/anti-parasitic inhibitors have not only been used against bacterial infections, but later reports have also shown them to work against deadly viruses such as SARS-CoV2. This key structural and inhibitory information is certain to help in the discovery of specific and potent substitute therapeutic drugs and the development of experimental procedures against human infection.

中文翻译：

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β-内酰胺酶蛋白的分子基础通过比较建模，药物筛选和分子动力学研究来了解β-内酰胺抗生素的耐药性。

通常，β-内酰胺酶（ampC）会引起病原菌对β-内酰胺抗生素产生抗药性。属于肠杆菌科的蛋白酶族的摩根氏摩根氏菌是革兰氏阴性杆菌。革兰氏阴性细菌是人类人群中过度表达对β-内酰胺抗生素耐药性的关键问题药物。这些经过实验研究的β-内酰胺类抗生素仍缺乏抗药性的关键信息和机理。ampC蛋白的结构信息是未知的，并且研​​究不足。因此，需要一个小时才能找到有效的抑制剂。在我们的研究中，对三维结构的预测使用比较建模方法进行了来自摩根氏摩根氏菌的ampC蛋白。通过100 ns分子动力学模拟运行，预测的结构得到了能量稳定，并绘制了功能构象。此外，Ramachandran图还显示该模型是立体化学稳定的，在核心允许区域下发现了大多数残基。然后确认了用几种经过实验测试的抑制剂进行的药物筛选，以检查其对ampC的活性使用AutoDock工具的蛋白质。结果表明，OncoglabrinolC分子是最佳抑制剂（在21个药物分子中），结合亲和力为− 11.44 kcal / mol。抗细菌/抗寄生虫抑制剂不仅用于抵抗细菌感染，而且后来的报告也显示它们可对抗致命病毒（例如SARS-CoV2）起作用。这种关键的结构和抑制信息必定有助于发现特定且有效的替代治疗药物，以及开发针对人类感染的实验程序。