Exploring the correlation between the folding rates of proteins and the entanglement of their native states
Exploring the correlation between the folding rates of proteins and the entanglement of their native states
复制标题
DOI：
10.1088/1751-8121/aa97e7
复制
发表时间：
2017-12-15
影响因子：
2.1
通讯作者：
Trovato, Antonio
中科院分区：
文献类型：
--
作者：
Baiesi, Marco;Orlandini, Enzo;Trovato, Antonio
蛋白质向其天然状态折叠是一个相当复杂的过程。然而，有经验证据表明，折叠时间与接触顺序相关，这是蛋白质天然状态空间组织的一个简单度量。接触顺序与由接触的氨基酸形成的主链环的平均长度有关。在这里，我们认为，折叠动力学也可以受到纠缠的影响，环可能会经历在整个三维蛋白质结构。为了探索这种可能性，我们引入了一种新的描述符，我们称之为“最大链内接触纠缠”。具体来说，我们测量的最大高斯纠缠蛋白质的任何环状部分和任何其他非重叠的子链相同的蛋白质，这是很容易计算的离散线积分的坐标上的C-α原子之间。通过分析两状态和多状态文件夹的实验数据集，我们表明，新的索引也是一个很好的预测的折叠率。此外，由于它与以前的方法只有部分相关性，因此可以与它们集成以产生更准确的预测。
The folding of a protein towards its native state is a rather complicated process. However, there is empirical evidence that the folding time correlates with the contact order, a simple measure of the spatial organization of the native state of the protein. Contact order is related to the average length of the main chain loops formed by amino acids that are in contact. Here we argue that folding kinetics can also be influenced by the entanglement that loops may undergo within the overall three-dimensional protein structure. In order to explore such a possibility, we introduce a novel descriptor, which we call 'maximum intrachain contact entanglement'. Specifically, we measure the maximum Gaussian entanglement between any looped portion of a protein and any other non-overlapping subchain of the same protein, which is easily computed by discretized line integrals on the coordinates of the C-alpha atoms. By analyzing experimental data sets of two-state and multi-state folders, we show that the new index is also a good predictor of the folding rate. Moreover, being only partially correlated with previous methods, it can be integrated with them to yield more accurate predictions.