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. 2011 Apr 20;6(4):e19001.
doi: 10.1371/journal.pone.0019001.

GPS-CCD: A Novel Computational Program for the Prediction of Calpain Cleavage Sites

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Free PMC article

GPS-CCD: A Novel Computational Program for the Prediction of Calpain Cleavage Sites

Zexian Liu et al. PLoS One. .
Free PMC article

Abstract

As one of the most essential post-translational modifications (PTMs) of proteins, proteolysis, especially calpain-mediated cleavage, plays an important role in many biological processes, including cell death/apoptosis, cytoskeletal remodeling, and the cell cycle. Experimental identification of calpain targets with bona fide cleavage sites is fundamental for dissecting the molecular mechanisms and biological roles of calpain cleavage. In contrast to time-consuming and labor-intensive experimental approaches, computational prediction of calpain cleavage sites might more cheaply and readily provide useful information for further experimental investigation. In this work, we constructed a novel software package of GPS-CCD (Calpain Cleavage Detector) for the prediction of calpain cleavage sites, with an accuracy of 89.98%, sensitivity of 60.87% and specificity of 90.07%. With this software, we annotated potential calpain cleavage sites for hundreds of calpain substrates, for which the exact cleavage sites had not been previously determined. In this regard, GPS-CCD 1.0 is considered to be a useful tool for experimentalists. The online service and local packages of GPS-CCD 1.0 were implemented in JAVA and are freely available at: http://ccd.biocuckoo.org/.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The prediction performance of GPS-CCD 1.0.
The self-consistency validation, leave-one-out validation and 4-, 6-, 8-, 10-fold cross-validations were calculated. The Receiver Operating Characteristic (ROC) curves and AROC values were also performed.
Figure 2
Figure 2. The screen snapshot of GPS-CCD software.
A high threshold was chosen as the default cut-off. The human cyclin-dependent kinase 4 inhibitor D/CDKN2D (P55273) is presented as an example.
Figure 3
Figure 3. Comparison of GPS 2.0, GPS 1.1 , PoPS , , SitesPrediction and CaMPDB .
The leave-one-out performances were calculated for GPS 2.0, GPS 1.1 and PoPS. We calculated the accuracy of SitesPrediction by directly submitting the benchmark data set for the prediction. (A) The data set contains 368 cleavage sites in 130 unique substrates; (B) For CaMPDB, we took 267 cleavage sites in 104 proteins from its website . The highest AROC value in CaMPDB was 0.801.
Figure 4
Figure 4. Applications of GPS-CCD 1.0.
Here we predicted the potential calpain cleavage sites in the experimentally identified calpain substrates with a default threshold. (A) The human NCS1 (P62166); (B) The human PEBP (P30086); (C) The Rat Ptpn5 (P35234); (D) The Aplysia atypical PKC (C3VIX7).

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