Biomolecular Physics and Modeling Group, School of Physics, Huazhong University of Science and Technology, Wuhan, China.
Proteins. 2021 Jul;89(7):832-844. doi: 10.1002/prot.26062. Epub 2021 Feb 23.
Protein folding is a popular topic in the life science. However, due to the limited sampling ability of experiments and simulations, the general folding mechanism is not yet clear to us. In this work, we study the folding of the N-terminal domain of ribosomal protein L9 (NTL9) in detail by a mixing replica exchange molecular dynamics method. The simulation results are close to previous experimental observations. According to the Markov state model, the folding of the protein follows a nucleation-condensation path. Moreover, after the comparison to its 39-residue β-α-β motif, we find that the helix at the C-terminal has a great influence on the folding process of the intact protein, including the nucleation of the key residues in the transition state ensemble and the packing of the hydrophobic residues in the native state.
蛋白质折叠是生命科学中的一个热门话题。然而，由于实验和模拟的采样能力有限，我们还不清楚蛋白质的一般折叠机制。在这项工作中，我们通过混合 replica exchange 分子动力学方法详细研究了核糖体蛋白 L9 的 N 端结构域（NTL9）的折叠。模拟结果与之前的实验观察结果非常吻合。根据马科夫状态模型，蛋白质的折叠遵循成核-凝聚路径。此外，与它的 39 个残基的 β-α-β 基序进行比较后，我们发现 C 端的螺旋对完整蛋白质的折叠过程有很大的影响，包括在过渡态集合中关键残基的成核和在天然状态下疏水残基的堆积。
