Huang Jitao T, Huang Wei, Huang Shanran R, Li Xin
Department of Chemistry and State Key Laboratory of EOC, College of Chemistry, Nankai University, Tianjin, 300071, China.
Proteins. 2014 Oct;82(10):2375-82. doi: 10.1002/prot.24599. Epub 2014 Jun 9.
Proteins fold by either two-state or multistate kinetic mechanism. We observe that amino acids play different roles in different mechanism. Many residues that are easy to form regular secondary structures (α helices, β sheets and turns) can promote the two-state folding reactions of small proteins. Most of hydrophilic residues can speed up the multistate folding reactions of large proteins. Folding rates of large proteins are equally responsive to the flexibility of partial amino acids. Other properties of amino acids (including volume, polarity, accessible surface, exposure degree, isoelectric point, and phase transfer energy) have contributed little to folding kinetics of the proteins. Cysteine is a special residue, it triggers two-state folding reaction and but inhibits multistate folding reaction. These findings not only provide a new insight into protein structure prediction, but also could be used to direct the point mutations that can change folding rate.
蛋白质通过两态或多态动力学机制进行折叠。我们观察到氨基酸在不同机制中发挥着不同的作用。许多易于形成规则二级结构（α螺旋、β折叠和转角）的残基能够促进小蛋白质的两态折叠反应。大多数亲水残基能够加速大蛋白质的多态折叠反应。大蛋白质的折叠速率对部分氨基酸的柔韧性同样有反应。氨基酸的其他特性（包括体积、极性、可及表面积、暴露程度、等电点和相转移能）对蛋白质的折叠动力学贡献很小。半胱氨酸是一种特殊的残基，它引发两态折叠反应但抑制多态折叠反应。这些发现不仅为蛋白质结构预测提供了新的见解，还可用于指导能够改变折叠速率的点突变。
