基于多因素耦合参数拟合蛋白质折叠速率

Protein folding rate fitting based on multi-factor coupled parameters

从蛋白质天然态的序列和结构中,提取了规则二级结构数、氨基酸类型加权长程序、单位链长回转半径和向列序等4个参数,这些参数分别表征了蛋白质的大小、拓扑、氨基酸组成、几何形状和规则二级结构排列有序性。将4个参数耦合在一起,构建了耦合参数与折叠速率之间的幂律依赖方程。在包含155个蛋白质折叠速率的实验数据集上,采用极大似然估计确定了方程的待定参数。结果表明:耦合参数实现了对折叠速率80%的拟合优度,而且95%的蛋白质折叠速率在预测值的50倍以内,对于跨越9个数量级的折叠速率数据,耦合参数捕获了影响折叠速率的主要因素。

The four parameters including the number of regular secondary structures,the weighted long-range order of amino acid types,the radius of gyration per unit chain length and the nematic order were extracted from the sequence and structure of the native state of the protein.These parameters characterize the size,topology,amino acid composition,geometry and the ordered degree of secondary structure arrangement of the protein,respectively.The four parameters were coupled together to construct a powerlaw dependence equation between the coupling parameters and the folding rate.On an experimental data set containing 155 protein folding rates,the parameters to be determined for the equations were determined using maximum likelihood estimation.The results show that the coupling parameter achieves an 80%goodness of fit to the folding rate and that 95%of the protein folding rates are within 50-fold of the predicted value,and for the folding rate data spanning nine orders of magnitude,the coupling parameter captures the major factors affecting the folding rate.