COMPUTATIONAL INSIGHTS INTO BACTERIAL RESISTANCE: ANTIBIOTICS

我们正在研究β-内酰胺类药物的内在反应性 了解其作用和失活的机制 β-内酰胺酶和青霉素结合蛋白。从头算量子 使用可极化连续介质模型的力学计算 利用估计的溶剂化效应分析了 部分β-内酰胺类药物和SIMPLE的水解和甲烷解 阿米德。四元环应变、还原型酰胺的作用 共振、取代基和环融合对水解性和 甲醇介导的这些化合物的水解性已经通过 气相和气相中相应反应路径的重建 解决方案。对这种反应性的洞察可能被证明是非常有用的 新型高效抗菌剂的设计。计算机图形学 实验室设施已被用于可视化 分子。

We are investigating the intrinsic reactivity of beta-lactams for understanding the mechanisms of action and inactivation of beta-lactamases and penicillin-binding proteins. Ab initio quantum mechanical calculations using a polarizable continuum model to estimate solvation effects have been utilized to analyze the hydrolysis and methanolysis of selected beta-lactams and simple amides. The roles of four-membered ring strain, reduced amide resonance, substituent and ring fusion effects on hydrolysis and methanol-mediated hydrolysis of these compounds have been studied by reconstructing the corresponding reaction pathways in gas and solution. Insights into this reactivity could prove very useful in the design of novel potent antimicrobials. The Computer Graphics Laboratory facilities has been used for visualization of the molecules.