Gräter Frauke, Li Wenjin
Heidelberg Institute for Theoretical Studies, Heidelberg, Germany.
Interdisciplinary Center for Scientific Computing, Heidelberg University, Heidelberg, Germany.
Methods Mol Biol. 2019;1967:87-113. doi: 10.1007/978-1-4939-9187-7_6.
Biochemical and structural data reveal important aspects of the properties and function of a protein disulphide bond. Molecular dynamics simulations can complement this experimental data and can yield valuable insights into the dynamical behavior of the disulphide bond within the protein environment. Due to the increasing accuracy of the underlying energetic description and the increasing computational power at hand, such simulations have now reached a level, at which they can also make quantitative and experimentally testable predictions. We here give an overview of the computational methods used to predict functional aspects of protein disulphides, including the prestress, protein allosteric effects upon thiol/disulphide exchange, and disulphide redox potentials. We then outline in detail the use of free-energy perturbation methods to calculate the redox potential of a protein disulphide bond of interest. In a step-by-step protocol, we describe the workflow within the MD suite Gromacs, including practical advice on the simulation setup and choice of parameters. For other disulphide-related simulation methods, we refer to resources available online.
生化和结构数据揭示了蛋白质二硫键性质和功能的重要方面。分子动力学模拟可以补充这些实验数据，并能对蛋白质环境中二硫键的动力学行为产生有价值的见解。由于基础能量描述的准确性不断提高以及现有计算能力不断增强，此类模拟如今已达到一个水平，即它们还能做出定量且可通过实验验证的预测。我们在此概述用于预测蛋白质二硫键功能方面的计算方法，包括预应力、蛋白质对硫醇/二硫键交换的变构效应以及二硫键氧化还原电位。然后我们详细概述使用自由能微扰方法来计算感兴趣的蛋白质二硫键的氧化还原电位。在一个逐步的方案中，我们描述了MD软件包Gromacs中的工作流程，包括关于模拟设置和参数选择的实用建议。对于其他与二硫键相关的模拟方法，我们参考在线可用资源。
