The Prediction of Calpain Cleavage Sites with the mRMR and IFS Approaches

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1. Introduction

Calpains are an important family of the C a 2 + -dependent cysteine proteases which catalyze the limited proteolysis of many specific substrates [1, 2]. Probably, 16 known calpain isoform genes are founded in humans. Then, 14 genes encoded proteins have cysteine protease domains, and the other 2 genes that encode some regulatory proteins are associated with some catalytic subunits forming heterodimeric proteases [3, 4]. Calpains play crucial roles in basic physiological and pathological processes, including the regulation of gene expression, signal transduction, cell death and apoptosis, remodeling cytoskeletal attachments during cell fusion or motility, and cell cycle progression [3–5]. Moreover, calpain aberrancies frequently lead to a variety of diseases and cancers [6]. As we know, traditional experimental identification and characterization of calpain cleavage sites are labor-intensive and expensive. Recently, calpain cleavage sites prediction attracts more and more attention, and more and more studies have understood its regulatory roles and molecular mechanisms of calpain cleavage.

In recent years, many computational methods were developed to predict calpain cleavage sites. In the paper [7], Tompa et al. selected 49 calpain substrates with a total of 106 sequentially identified cleavage sites from the literature. They determined the amino acid preferences around the cleavage bond with 11-mer peptide, and they synthesized a short peptide of TPLKSPPPSPR to be a superior substrate of calpain. Then, Boyd et al. developed PoPS online tool to predict protease specificity [8, 9]. And the site prediction based on the frequency and substitution matrix scoring strategy predicted Calpain 1 and 2 specific cleavage sites [10]. Recently, Liu et al. developed a new computational program for the prediction of calpain cleavage sites. With the previously released algorithm of GPS (Group-based Prediction System), they designed a novel software package of GPS-CCD (Calpain Cleavage Detector) for prediction of...