School of Life Sciences, University of Technology Sydney, Ultimo, NSW, Australia.
School of Mechanical and Mechatronic Engineering, University of Technology Sydney, Ultimo, NSW, Australia.
Methods Mol Biol. 2022;2402:103-121. doi: 10.1007/978-1-0716-1843-1_9.
The lung surfactant monolayer (LSM) is a thin layer of lipids and proteins that forms the air/water interface of the alveoli. The primary function of the LSM is to reduce the surface tension at the air/water interface during breathing. The LSM also forms the main biological barrier for any inhaled particles, including drugs, to treat lung diseases. Elucidating the mechanism by which these drugs bind to and absorb into the LSM requires a molecular-level understanding of any drug-induced changes to the morphology, structure, and phase changes of the LSM.Molecular dynamics simulations have been used extensively to study the structure and dynamics of the LSM. The monolayer is usually simulated in at least two states: the compressed state, mimicking exhalation, and the expanded state, mimicking inhalation. In this chapter, we provide detailed instructions on how to set up, run, and analyze coarse-grained MD simulations to study the concentration-dependent effect of a sterol drug on the LSM, both in the expanded and compressed state.
肺表面活性剂单层（LSM）是一层薄薄的脂质和蛋白质，形成肺泡的气/水界面。LSM 的主要功能是在呼吸过程中降低气/水界面的表面张力。LSM 还为任何吸入的颗粒（包括药物）形成主要的生物屏障，以治疗肺部疾病。阐明这些药物与 LSM 结合并吸收进入 LSM 的机制需要对药物诱导的 LSM 形态、结构和相变化有分子水平的理解。分子动力学模拟已被广泛用于研究 LSM 的结构和动力学。单层通常模拟至少两种状态：模拟呼气的压缩状态和模拟吸气的扩展状态。在本章中，我们提供了详细的说明，介绍如何设置、运行和分析粗粒度 MD 模拟，以研究甾醇药物在扩展和压缩状态下对 LSM 的浓度依赖性影响。
