Determination of protein folding kinetic types using sequence and predicted secondary structure and solvent accessibility
Determination of protein folding kinetic types using sequence and predicted secondary structure and solvent accessibility
复制标题
使用序列和预测的二级结构和溶剂可及性确定蛋白质折叠动力学类型
DOI：
10.1007/s00726-010-0805-y
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发表时间：
2012-01-01
期刊：
影响因子：
3.5
通讯作者：
Kurgan, Lukasz
中科院分区：
文献类型：
--
作者：
Zhang, Hua;Zhang, Tuo;Kurgan, Lukasz
蛋白质通过两态（TS）折叠，没有可见的中间产物，或者通过至少一个中间过程进行多态（MS）折叠。我们通过引入一种新的基于序列的折叠类型预测器FOKIT来分析决定折叠类型的序列衍生因素。该方法实现了一个具有六个输入特征的逻辑回归模型，这些特征混合了氨基酸组成信息，并预测了二级结构和溶剂可及性。通过对四个基准数据集的样本外测试，FOKIT提供了平均马修斯相关系数（MCC）在0.58至0.91之间的预测。这些结果被证明是有竞争力的，或者比四个现代预测的结果更好。我们还表明，在预测与用于构建模型的链具有低相似性的链时，FOKIT优于这些方法，这是一个重要的优势，因为注释链的数量有限。我们证明包含溶剂可及性有助于折叠动力学类型的区分，并且三个特征构成了区分TS和MS文件夹的统计显著标记。我们发现，暴露的色氨酸和埋藏的亮氨酸含量的增加是MS折叠的标志，这表明某些疏水残基的暴露/埋藏可能在折叠中间体的形成中起重要作用。我们的结论得到了两个案例研究的支持。
Proteins fold through a two-state (TS), with no visible intermediates, or a multi-state (MS), via at least one intermediate, process. We analyze sequence-derived factors that determine folding types by introducing a novel sequence-based folding type predictor called FOKIT. This method implements a logistic regression model with six input features which hybridize information concerning amino acid composition and predicted secondary structure and solvent accessibility. FOKIT provides predictions with average Matthews correlation coefficient (MCC) between 0.58 and 0.91 measured using out-of-sample tests on four benchmark datasets. These results are shown to be competitive or better than results of four modern predictors. We also show that FOKIT outperforms these methods when predicting chains that share low similarity with the chains used to build the model, which is an important advantage given the limited number of annotated chains. We demonstrate that inclusion of solvent accessibility helps in discrimination of the folding kinetic types and that three of the features constitute statistically significant markers that differentiate TS and MS folders. We found that the increased content of exposed Trp and buried Leu are indicative of the MS folding, which implies that the exposure/burial of certain hydrophobic residues may play important role in the formation of the folding intermediates. Our conclusions are supported by two case studies.