COMPUTATIONAL INSIGHTS INTO BACTERIAL RESISTANCE: ANTIBIOTICS

我们正在研究β-内酰胺的固有反应性， 了解的作用和失活的机制， β-内酰胺酶和青霉素结合蛋白。 从头量子 力学计算使用极化连续模型， 估计溶剂化效应已被用来分析 选择β-内酰胺的水解和甲醇分解， 酰胺。 四元环张力、还原酰胺的作用 共振，取代基和环融合对水解的影响， 甲醇介导的这些化合物的水解已经被研究， 在气体中重构相应的反应路径， 溶液 对这种反应性的深入了解可以证明非常有用， 新型强效抗菌剂的设计。 计算机图形 实验室设施已被用于可视化的 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.