BACKGROUND One of the main concerns of the modern medicine is the frightening spread of antimicrobial resistance caused mainly by the misuse of antibiotics. The researchers worldwide are actively involved in the search for new classes of antibiotics, and for the modification of known molecules in order to face this threatening problem. We have applied a computational approach to predict the interactions between a new cephalosporin derivative containing an additional β-lactam ring with different substituents, and several serine β-lactamases representative of the different classes of this family of enzymes. RESULTS The results of the simulations, performed by using a covalent docking approach, has shown that this compound, although able to bind the selected β-lactamases, has a different predicted binding score for the two β-lactam rings, suggesting that one of them could be more resistant to the attack of these enzymes and stay available to perform its bactericidal activity. CONCLUSIONS The detailed analysis of the complexes obtained by these simulations suggests possible hints to modulate the affinity of this compound towards these enzymes, in order to develop new derivatives with improved features to escape to degradation.

中文翻译：

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新型头孢菌素衍生物与β-内酰胺酶相互作用的计算分析。

背景技术现代医学的主要关注之一是主要由滥用抗生素引起的令人恐惧的抗药性扩散。世界各地的研究人员都在积极地寻找新型抗生素，并对已知分子进行修饰以应对这一威胁性问题。我们已经应用了一种计算方法来预测新的头孢菌素衍生物之间的相互作用，所述头孢菌素衍生物含有另外的具有不同取代基的β-内酰胺环，以及代表该酶家族不同类别的几种丝氨酸β-内酰胺酶。结果使用共价对接方法进行的模拟结果表明，该化合物虽然能够结合所选的β-内酰胺酶，但对两个β-内酰胺环的预测结合分数不同，提示其中一种可能对这些酶的攻击具有更强的抵抗力，并保持其杀菌活性。结论对通过这些模拟得到的复合物的详细分析表明，可能存在调节该化合物对这些酶的亲和力的提示，以便开发出具有改进特性的新衍生物，以逃避降解。