Tyoe Owen, Zhang Kai, Diao Jiajie
Department of Physics, University of Cincinnati College of Arts and Sciences, Cincinnati, OH, USA.
Department of Biochemistry, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Methods Mol Biol. 2025;2887:53-68. doi: 10.1007/978-1-0716-4314-3_3.
The soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein complex drives membrane fusion, and this process is further aided by accessory proteins, including complexin and α-synuclein. To understand the molecular mechanism underlying membrane fusion, we introduce an all-atom molecular dynamics (MD) simulation method. This method is used to understand and predict the conformations of protein and lipids, membrane geometry, and their interaction at femtosecond precision, by describing complex chemical systems with atomic models. Simulation results reveal information on distinct membrane fusion stages, including docking, hemifusion, and kiss-and-run fusion. Here, we introduce the simulation workflow, consisting of pre-MD construction, pre-MD setup in GROMACS, MD in GROMACS, and analysis.
可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白复合物驱动膜融合，包括复合体蛋白和α-突触核蛋白在内的辅助蛋白进一步促进了这一过程。为了理解膜融合背后的分子机制，我们引入了一种全原子分子动力学（MD）模拟方法。该方法通过用原子模型描述复杂的化学系统，以飞秒精度来理解和预测蛋白质与脂质的构象、膜几何形状及其相互作用。模拟结果揭示了不同膜融合阶段的信息，包括对接、半融合和吻痕-运行融合。在此，我们介绍模拟工作流程，包括MD前构建、GROMACS中的MD前设置、GROMACS中的MD以及分析。
