Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks
Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks
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DOI：
10.1002/pro.5560051107
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发表时间：
1996-11-01
期刊：
影响因子：
8
通讯作者：
Brunak, S
中科院分区：
文献类型：
--
作者：
Blom, N;Hansen, J;Brunak, S
小核糖核酸病毒蛋白水解酶负责病毒多蛋白的成熟裂解，但也催化细胞靶标的降解。利用图形可视化技术和神经网络算法，我们研究了两种蛋白酶2A(PRO)和3C(PRO)的序列特异性。还检测了VP0(产生VP2和VP4)的切割，这种切割是由一种迄今未知的蛋白酶执行的。与一种新的表面暴露预测算法相结合，我们的神经网络方法成功地区分了已知的切割位点和非切割位点，并产生了对这些位点共同特征的更一致的定义。该方法能够预测实验确定的细胞蛋白质的裂解位点。我们提出了一份哺乳动物和其他蛋白质的清单，这些蛋白质被预测为病毒蛋白酶的可能靶标。这些蛋白质是否真的被切割还有待实验验证。此外，我们报告了在蛋白质数据库中检测到的几个错误。用于预测微小核糖体病毒蛋白水解酶切割位点的计算机服务器可通过电子邮件地址netPicoRNA@cbs.dtu.dk公开获得，或通过WWW在http://www.cbs.dtu.dk/services/NetPicoRNA/.获得
Picornaviral proteinases are responsible for maturation cleavages of the viral polyprotein, but also catalyze the degradation of cellular targets. Using graphical visualization techniques and neural network algorithms, we have investigated the sequence specificity of the two proteinases 2A(pro) and 3C(pro). The cleavage of VP0 (giving rise to VP2 and VP4), which is carried out by a so-far unknown proteinase, was also examined. In combination with a novel surface exposure prediction algorithm, our neural network approach successfully distinguishes known cleavage sites from noncleavage sites and yields a more consistent definition of features common to these sites. The method is able to predict experimentally determined cleavage sites in cellular proteins. We present a list of mammalian and other proteins that are predicted to be possible targets for the viral proteinases. Whether these proteins are indeed cleaved awaits experimental verification. Additionally, we report several errors detected in the protein databases.A computer server for prediction of cleavage sites by picornaviral proteinases is publicly available at the e-mail address NetPicoRNA@cbs.dtu.dk or via WWW at http://www.cbs.dtu.dk/services/NetPicoRNA/.