Settanni Giovanni
Physics Department, Johannes Gutenberg Universität, Staudingerweg 9, 55128, Mainz, Germany,
Methods Mol Biol. 2015;1215:289-306. doi: 10.1007/978-1-4939-1465-4_13.
The interplay between simulations and experiments of protein folding has largely contributed to the elucidation of many important aspects of the phenomenon. In this chapter, I briefly describe the experiments which provide information on the kinetics of the protein folding process, and help to characterize the folding transition state. Then, I show how to probe the kinetics of protein folding using molecular dynamics simulations, how to compare the simulations with the experiments and how to help and rationalize the latter, ultimately offering a molecular picture of the process. After the production of suitable molecular dynamics simulation data in the form of trajectories, the procedure involves sequentially the identification of the stable states of the protein, the identification of the transition pathways connecting the stable states, the identification of the transition state conformations, comparison with experimental results, and finally, the identification of the molecular determinants or reaction coordinates of the folding process, that is, the features that clearly help distinguishing the transition state from the stable states.
蛋白质折叠的模拟与实验之间的相互作用在很大程度上有助于阐明该现象的许多重要方面。在本章中，我简要描述了一些实验，这些实验提供了有关蛋白质折叠过程动力学的信息，并有助于表征折叠过渡态。然后，我展示了如何使用分子动力学模拟来探究蛋白质折叠的动力学，如何将模拟结果与实验进行比较以及如何辅助并合理解释实验结果，最终呈现出该过程的分子图景。在以轨迹形式生成合适的分子动力学模拟数据之后，该过程依次包括确定蛋白质的稳定状态、确定连接稳定状态的过渡途径、确定过渡态构象、与实验结果进行比较，最后确定折叠过程的分子决定因素或反应坐标，即那些有助于清晰区分过渡态与稳定状态的特征。
