Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia; Institute of Mathematical Problems of Biology, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
Proteins. 2013 Sep;81(9):1527-41. doi: 10.1002/prot.24301. Epub 2013 Jun 20.
Despite the large number of publications on three-helix protein folding, there is no study devoted to the influence of handedness on the rate of three-helix protein folding. From the experimental studies, we make a conclusion that the left-handed three-helix proteins fold faster than the right-handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three-helix proteins (four right-handed and four left-handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary-structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left-handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right-handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three-helix proteins (238 right- and 94 left-handed). From our analysis, we found that the left-handed three-helix proteins have some less-dense packing that should result in faster folding for some proteins as compared to the case of right-handed proteins.
尽管有大量关于三螺旋蛋白折叠的出版物，但没有研究专门探讨手性对三螺旋蛋白折叠速度的影响。从实验研究中，我们得出结论，左手性三螺旋蛋白比右手性三螺旋蛋白折叠得更快。这一差异可能是什么原因造成的呢？本文提出的一个重要问题是，蛋白质折叠的建模是否能够捕捉到具有相似结构但折叠机制不同的蛋白质折叠速度之间的差异。为了回答这个问题，我们使用蒙特卡罗和动态编程方法对 8 种三螺旋蛋白（4 种右手性和 4 种左手性）的折叠进行了建模。这些研究使我们能够确定这些结构域中二级结构元素和对折叠重要的氨基酸残基的折叠顺序。所得数据彼此之间以及与实验数据高度相关。对这些蛋白质的结构分析表明，左手性结构域的每个残基的接触数和横截面积比右手性结构域小。这可能是观察到的事实的一个解释。对于由 332 种三螺旋蛋白（238 种右手性和 94 种左手性）组成的大型数据集也观察到了同样的趋势。从我们的分析中，我们发现，与右手性蛋白质相比，左手性三螺旋蛋白质的堆积密度较小，这应该导致某些蛋白质的折叠速度更快。
