Verdino Anna, Zollo Felicia, De Rosa Margherita, Soriente Annunziata, Hernández-Martínez Miguel Ángel, Marabotti Anna
Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
University of Rennes 1, Campus de Beaulieu, 35042 Rennes CEDEX, Rennes, France.
BMC Struct Biol. 2018 Oct 4;18(1):13. doi: 10.1186/s12900-018-0092-5.
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.
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.
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.
现代医学的主要关注点之一是主要由抗生素滥用导致的令人担忧的抗菌药物耐药性传播。世界各地的研究人员都在积极寻找新型抗生素，并对已知分子进行修饰，以应对这一威胁性问题。我们应用了一种计算方法来预测一种含有额外β-内酰胺环且带有不同取代基的新型头孢菌素衍生物与该酶家族不同类别中的几种丝氨酸β-内酰胺酶之间的相互作用。
使用共价对接方法进行模拟的结果表明，该化合物虽然能够与所选的β-内酰胺酶结合，但两个β-内酰胺环的预测结合分数不同，这表明其中一个可能对这些酶的攻击更具抗性，并能保持其杀菌活性。
对这些模拟得到的复合物的详细分析表明了一些可能的线索，可用于调节该化合物对这些酶的亲和力，以便开发出具有更好特性以避免降解的新衍生物。
