Cleavage site analysis in picornaviral polyproteins: discovering
cellular targets by neural networks.
Center for Biological Sequence Analysis, Technical University of Denmark
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 2Apro and 3Cpro.
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.