Predikin and PredikinDB: a computational framework for the prediction of protein kinase peptide specificity and an associated database of phosphorylation sites

Here, we describe a new version of Predikin, completely revised and rewritten as a modular framework that provides multiple enhancements compared with the original. Predikin now consists of two components: (i) PredikinDB, a database of phosphorylation sites that links substrates to kinase sequences and (ii) a Perl module, which provides methods to classify protein kinases, reliably identify substrate-determining residues, generate scoring matrices and score putative phosphorylation sites in query sequences. The performance of Predikin as measured using receiver operator characteristic (ROC) graph analysis equals or surpasses that of existing comparable methods. The Predikin website has been redesigned to incorporate the new features.New features in Predikin include the use of SQL queries to PredikinDB to generate predictions, scoring of predictions, more reliable identification of substrate-determining residues and putative phosphorylation sites, extended options to handle protein kinase and substrate data and an improved web interface. The new features significantly enhance the ability of Predikin to analyse protein kinases and their substrates. Predikin is available at http://predikin.biosci.uq.edu.au webcite.The post-translational modification of proteins by phosphorylation of serine, threonine or tyrosine residues is a ubiquitous process in cellular regulation. Protein kinases, the enzymes responsible for protein phosphorylation, make up almost 2% of protein-encoding genes in the human genome [1] and an estimated 30–50% of human proteins are phosphorylated [2]. Protein kinases and their substrates regulate essentially all cellular processes through complex regulatory networks, in which phosphorylated proteins act as switches that tune the response of the cell to environmental stimuli. Defects in these networks result in a variety of disease states making protein kinases important targets for drug design [3].In general, a protein kinase acts on a discrete set of