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

打破抗菌素耐药性的铠甲：基于分子水平对其机制的理解合理设计抗菌肽

• 批准号: 1953149
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1953149
• 关键词: Breaking; armour; antimicrobial; resistance; Rational

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.

抗菌素耐药性的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抗药性，这将增加死亡率，并增加手术引起的并发症数量。一种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细菌外膜模型来揭示一系列抗菌肽的作用机制。特别关注的将是这些肽在双层内的聚集，而不是单肽和双层之间的相互作用。该项目将使用原子级和粗粒度的分子动力学模拟以及原子力显微镜来实现这一点。该项目的新颖性在于最近开发的粗粒度模型可以提供的模拟规模，这些模型目前还没有得到严格的验证，也没有与高浓度的多肽一起使用。