Department of Chemical Engineering, Indian Institute of Science, Bengaluru, India.
Centre for Condensed Matter Theory, Department of Physics, Indian Institute of Science, Bengaluru, India.
Methods Enzymol. 2021;649:461-502. doi: 10.1016/bs.mie.2021.01.021. Epub 2021 Feb 27.
Pore forming toxins (PFTs) are virulent proteins released by several species, including many strains of bacteria, to attack and kill host cells. In this article, we focus on the utility of molecular dynamics (MD) simulations and the molecular insights gleaned from these techniques on the pore forming pathways of PFTs. In addition to all-atom simulations which are widely used, coarse-grained MARTINI models and structure-based models have also been used to study PFTs. Here, the emphasis is on methods and techniques involved while setting up, monitoring, and evaluating properties from MD simulations of PFTs in a membrane environment. We draw from several case studies to illustrate how MD simulations have provided molecular insights into protein-protein and protein-lipid interactions, lipid dynamics, conformational transitions and structures of both the oligomeric intermediates and assembled pore structures.
孔形成毒素 (PFTs) 是由多种物种释放的毒性蛋白，包括许多细菌株，用于攻击和杀死宿主细胞。在本文中，我们专注于分子动力学 (MD) 模拟的实用性以及这些技术在 PFT 孔形成途径上获得的分子见解。除了广泛使用的全原子模拟外，还使用了粗粒化 MARTINI 模型和基于结构的模型来研究 PFTs。在这里，重点是在膜环境中设置、监测和评估 MD 模拟中 PFT 性质时所涉及的方法和技术。我们从几个案例研究中汲取了经验，说明了 MD 模拟如何为蛋白质-蛋白质和蛋白质-脂质相互作用、脂质动力学、构象转变以及寡聚中间体和组装孔结构的结构提供分子见解。
