Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence.
Post-translational modifications (PTMs) occur on almost all proteins analyzed to date. The function of a modified protein is often strongly affected by these modifications and therefore increased knowledge about the potential PTMs of a target protein may increase our understanding of the molecular processes in which it takes part. High-throughput methods for the identification of PTMs are being developed, in particular within the fields of proteomics and mass spectrometry. However, these methods are still in their early stages, and it is indeed advantageous to cut down on the number of experimental steps by integrating computational approaches into the validation procedures. Many advanced methods for the prediction of PTMs exist and many are made publicly available. We describe our experiences with the development of prediction methods for phosphorylation and glycosylation sites and the development of PTM-specific databases. In addition, we discuss novel ideas for PTM visualization (exemplified by kinase landscapes) and improvements for prediction specificity (by using ESS--evolutionary stable sites). As an example, we present a new method for kinase-specific prediction of phosphorylation sites, NetPhosK, which extends our earlier and more general tool, NetPhos. The new server, NetPhosK, is made publicly available at the URL http://www.cbs.dtu.dk/services/NetPhosK/. The issues of underestimation, over-prediction and strategies for improving prediction specificity are also discussed.
Blom
Nikolaj
N
Center for Biological Sequence Analysis, The Technical University of Denmark, Lyngby, Denmark. nikob@cbs.dtu.dk
Sicheritz-Pontén
Thomas
T
Gupta
Ramneek
R
Gammeltoft
Steen
S
Brunak
Søren
S
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D006031:Glycosylation; D006801:Humans; D020407:Internet; D016571:Neural Networks, Computer; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D011506:Proteins; D011494:Protein Kinases