Institute of Protein Research, Russian Academy of Sciences, Group of Bioinformatics, 4 Institutskaya Str., Pushchino, Moscow Region 142290, Russia.
Proteins. 2012 Dec;80(12):2711-27. doi: 10.1002/prot.24156. Epub 2012 Sep 15.
The problem of protein self-organization is in the focus of current molecular biology studies. Although the general principles are understood, many details remain unclear. Specifically, protein folding rates are of interest because they dictate the rate of protein aggregation which underlies many human diseases. Here we offer predictions of protein folding rates and their correlation with folding nucleus sizes. We calculated free energies of the transition state and sizes of folding nuclei for 84 proteins and peptides whose other parameters were measured at the point of thermodynamic equilibrium between their unfolded and native states. We used the dynamic programming method where each residue was considered to be either as folded as in its native state or completely disordered. The calculated and measured folding rates showed a good correlation at the temperature mid-transition point (the correlation coefficient was 0.75). Also, we pioneered in demonstrating a moderate (-0.57) correlation coefficient between the calculated sizes of folding nuclei and the folding rates. Predictions made by different methods were compared. The established good correlation between the estimated free energy barrier and the experimentally found folding rate of each studied protein/peptide indicates that our model gives reliable results for the considered data set.
蛋白质自组织问题是当前分子生物学研究的焦点。尽管已经了解了一般原理，但仍有许多细节不清楚。具体来说，蛋白质折叠速率是人们关注的焦点，因为它们决定了蛋白质聚集的速度，而蛋白质聚集是许多人类疾病的基础。在这里，我们提供了蛋白质折叠速率及其与折叠核大小的相关性的预测。我们计算了 84 种蛋白质和肽的过渡态自由能和折叠核大小，这些蛋白质和肽的其他参数是在其未折叠状态和天然状态之间的热力学平衡点测量的。我们使用了动态规划方法，其中每个残基都被认为要么像在天然状态下那样折叠，要么完全无序。在温度过渡点（相关系数为 0.75），计算出的和测量出的折叠速率之间显示出很好的相关性。此外，我们率先证明了折叠核的计算大小与折叠速率之间存在中等（-0.57）的相关系数。比较了不同方法的预测结果。对于每个研究的蛋白质/肽，所估计的自由能势与实验发现的折叠速率之间建立的良好相关性表明，我们的模型对所考虑的数据集给出了可靠的结果。
