Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Infect Immun. 2021 Mar 17;89(4). doi: 10.1128/IAI.00703-20.
Although antimicrobial resistance is an increasingly significant public health concern, there have only been two new classes of antibiotics approved for human use since the 1960s. Understanding the mechanisms of action of antibiotics is critical for novel antibiotic discovery, but novel approaches are needed that do not exclusively rely on experiments. Molecular dynamics simulation is a computational tool that uses simple models of the atoms in a system to discover nanoscale insights into the dynamic relationship between mechanism and biological function. Such insights can lay the framework for elucidating the mechanism of action and optimizing antibiotic templates. Antimicrobial peptides represent a promising solution to escalating antimicrobial resistance, given their lesser tendency to induce resistance than that of small-molecule antibiotics. Simulations of these agents have already revealed how they interact with bacterial membranes and the underlying physiochemical features directing their structure and function. In this minireview, we discuss how traditional molecular dynamics simulation works and its role and potential for the development of new antibiotic candidates with an emphasis on antimicrobial peptides.
尽管抗菌药物耐药性是一个日益严重的公共卫生问题，但自 20 世纪 60 年代以来，仅有两类新的抗生素类药物获准用于人体。了解抗生素的作用机制对于新抗生素的发现至关重要，但需要新的方法，这些方法不应仅依赖于实验。分子动力学模拟是一种计算工具，它使用系统中原子的简单模型来发现纳米级的动态关系，从而深入了解机制与生物功能之间的关系。这些见解可以为阐明作用机制和优化抗生素模板奠定框架。抗菌肽是解决抗菌药物耐药性不断升级的一个有前途的解决方案，因为它们比小分子抗生素诱导耐药性的倾向更小。这些药物的模拟已经揭示了它们如何与细菌膜相互作用，以及指导它们的结构和功能的潜在理化特征。在这篇综述中，我们讨论了传统分子动力学模拟的工作原理，以及它在开发新抗生素候选药物方面的作用和潜力，重点是抗菌肽。
