Sequence-Based Prediction of Molecular Recognition Features in Disordered Proteins

Chun Fang, H. Yamana, T. Noguchi
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引用次数: 2

Abstract

Molecular recognition features (MoRFs) act as molecular switches in molecular-interaction network of the cell, and assumed to have relationship with the causes of many diseases. The importance of identifying MoRFs in disordered proteins is becoming increasingly apparent. So far, only a limited number of experimentally validated MoRFs is known, and there are few specialized tools for identifying MoRFs. Existing methods used many predicted results, such as predicted disorder probabilities, solvent accessibility and B-factors as features for prediction, or used MoRFs database directly for alignment to assist the prediction; however, their design are complex, and the performance is also affected largely by other predictors. In this study, we proposed a novel method, named as MFPSSMPred (Masked and Filtered PSSM based Prediction), which adopts a masking method to extract high local conservative features, and a filtering method to filter out low local conservative scores in position-specific scoring matrix (PSSMs) for prediction. All features are extracted from the sequences only. We compared our method with a traditional PSSM-based method and 9 other existed methods on a same test dataset. The experimental results showed that, our method achieved the best performance with AUC of 0.758. This study demonstrated that: 1) the flanking regions of MoRFs affected the plasticity of MoRFs; 2) MoRFs were flanked by less conserved residues; and 3) the revised PSSM was predictive features for identifying
基于序列的无序蛋白分子识别特征预测
分子识别特征(morf)是细胞分子相互作用网络中的分子开关,被认为与许多疾病的病因有关。在无序蛋白质中识别morf的重要性正变得越来越明显。到目前为止,已知的实验验证的morf数量有限,并且很少有专门的工具来识别morf。现有方法采用多种预测结果,如预测无序概率、溶剂可及性和b因子等作为预测特征,或直接使用morf数据库进行比对,辅助预测;然而,它们的设计是复杂的,性能也很大程度上受到其他预测因素的影响。在本研究中,我们提出了一种新的方法MFPSSMPred (masking and Filtered PSSM based Prediction),该方法采用掩模法提取局部保守性高的特征,采用滤波法过滤掉位置特定评分矩阵(position-specific scoring matrix, PSSM)中的局部保守性低的分数进行预测。所有特征仅从序列中提取。在同一测试数据集上,我们将该方法与传统的基于pssm的方法和其他9种现有方法进行了比较。实验结果表明,该方法在AUC为0.758时获得了最佳性能。研究结果表明:1)侧翼区域对复合材料的塑性有影响;2) morf两侧有保守性较低的残基;3)修订后的PSSM是识别的预测特征
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