Breaking the armour of antimicrobial resistance: Rational design of antimicrobial peptides based on molecular-level understanding of their mechanisms

抗菌药物耐药性问题将对现代世界产生广泛的影响。细菌正在对目前使用的抗生素产生耐药性，这将增加死亡率，并增加手术并发症的数量。一个建议的解决方案是专注于抗菌肽，因为它们对细菌的选择性较低。本项目将利用革兰氏阴性菌外膜模型揭示一系列抗菌肽的作用机制。特别的重点将放在这些肽在双分子层内的聚集，而不是单个肽和双分子层的相互作用。该项目将使用原子和粗粒度尺度的分子动力学模拟和原子力显微镜的混合来实现这一目标。该项目的新颖之处在于最近开发的粗粒度模型可以提供的模拟规模，这些模型目前尚未经过严格验证或与高浓度肽结合使用。

The issue of antibacterial resistance is one that will have wide reaching impact on the modern world. Bacteria are developing resistance to the antibiotics currently being used which will increase mortality rates and increase the number of complications as a result of surgeries. A proposed solution is to focus on antimicrobial peptides because of their less selective targeting of bacteria.This project will enlighten the mechanism of action of a range of antimicrobial peptides with a gram-negative bacteria outer membrane model. Particular focus will be on the aggregation of these peptides within the bilayer rather than the interaction of single peptides and the bilayer. The project will use a mixture of molecular dynamics simulations at the atomistic and coarse-grained scale and atomic force microscopy to achieve this.The novelty of the project is in the scale of the simulations that can be afforded by the recently developed coarse-grained models which have currently not been rigorously validated or used in conjunction with high concentrations of peptides.