Predicting Membrane-Active Peptide Dynamics in Fluidic Lipid Membranes.
Predicting Membrane-Active Peptide Dynamics in Fluidic Lipid Membranes.
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预测流体脂质膜中的膜活性肽动力学。
DOI：
10.1007/978-1-0716-1855-4_6
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Lu,TimothyK
中科院分区：
文献类型：
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作者：
Chen,CharlesH;Pepper,Karen;Ulmschneider,JakobP;Ulmschneider,MartinB;Lu,TimothyK
了解肽和脂质膜之间的相互作用不仅可以加速抗菌肽作为感染治疗方法的开发，还可以应用于寻找癌症和其他疾病的靶向疗法。然而，设计生物物理实验来研究柔性肽和流体脂膜之间的分子相互作用一直是一个持续的挑战。最近，随着硬件的进步、算法的改进和更准确的参数化（即力场），全原子分子动力学（MD）模拟已被用作“计算显微镜”来研究细胞膜中膜活性肽的分子相互作用和机制（Chen et al., Curr Opin Struct Biol 61:160–166, 2020；Ulmschneider and Ulmschneider, Acc Chem Res 51(5):1106–1116, 2018; Dror 等人, Annu Rev Biophys 41:429–452, 2012)。在本章中，我们描述如何利用 MD 模拟来预测和研究肽动力学，以及如何通过圆二色性、内源荧光探针、膜渗漏测定、电阻抗和等温滴定量热法验证模拟。经过实验验证的 MD 模拟开辟了一条从序列和结构开始进行肽设计并产生所需功能的新途径。
Understanding the interactions between peptides and lipid membranes could not only accelerate the development of antimicrobial peptides as treatments for infections but also be applied to finding targeted therapies for cancer and other diseases. However, designing biophysical experiments to study molecular interactions between flexible peptides and fluidic lipid membranes has been an ongoing challenge. Recently, with hardware advances, algorithm improvements, and more accurate parameterizations (i.e., force fields), all-atom molecular dynamics (MD) simulations have been used as a “computational microscope” to investigate the molecular interactions and mechanisms of membrane-active peptides in cell membranes (Chen et al., Curr Opin Struct Biol 61:160–166, 2020; Ulmschneider and Ulmschneider, Acc Chem Res 51(5):1106–1116, 2018; Dror et al., Annu Rev Biophys 41:429–452, 2012). In this chapter, we describe how to utilize MD simulations to predict and study peptide dynamics and how to validate the simulations by circular dichroism, intrinsic fluorescent probe, membrane leakage assay, electrical impedance, and isothermal titration calorimetry. Experimentally validated MD simulations open a new route towards peptide design starting from sequence and structure and leading to desirable functions.