N‐Terminal myristoylation predictions by ensembles of neural networks

Abstract

N-terminal myristoylation is a post-translational modification that causes the addition of a myristate to a glycine in the N-terminal end of the amino acid chain. This work presents neural network (NN) models that learn to discriminate myristoylated and nonmyristoylated proteins. Ensembles of 25 NNs and decision trees were trained on 390 positive sequences and 327 negative sequences. Experiments showed that NN ensembles were more accurate than decision tree ensembles. Our NN predictor evaluated by the leave-one-out procedure, obtained a false positive error rate equal to 2.1%. That was better than the PROSITE pattern for myristoylation for which the false positive error rate was 22.3%. On a recent version of Swiss-Prot (41.2), the NN ensemble predicted 876 myristoylated proteins, while 1150 proteins were predicted by the PROSITE pattern for myristoylation. Finally, compared to the well-known NMT predictor, the NN predictor gave similar results. Our tool is available under http://www.expasy.org/tools/myristoylator/myristoylator.html.

Annotation of microsporidian genomes using transcriptional signals

“…For post-translational modifications, we looked for GPI anchors (http://mendel.imp.ac.at/sat/gpi/gpi_server. html) 53 , myristoylation (http://web.expasy.org/myristoylator/) 54 , palmitoylation (http://csspalm.biocuckoo.org/) 55 and prenylation (http://mendel.imp.ac.at/sat/ PrePS/index.html) 56 .…”

Rapid detection, discovery, and identification of post‐translationally myristoylated proteins during apoptosis using a bio‐orthogonal azidomyristate analog

“…Since we showed that the myristoylation of short chimeric WT-ctPAK2-N 15 -EGFP and WT-Yes-N 11 -GFP can readily be detected using azidomyristate cell labeling and reaction with phosphinebiotin (Fig. 2), we first identified internal myristoylation sites adjacent to caspase cleavage sites using computational prediction analysis (23,24) and, second, incorporated these predicted NMT substrate sequences at the N terminus of EGFP at the cDNA level (Supplemental Table 2). Finally, using our nonradioactive azidomyristate labeling/ phosphine-biotin-based detection method, we assessed the myristoylation status of the chimeric EGFP proteins transiently expressed in COS-7 cells.…”

“…To do so, the complete carboxyl terminal sequences downstream of the caspase cleavage site were subjected to computational prediction analysis based on myristoylator and NMT-the Myr Predictor algorithms (23,24). Of more than 280 proteins identified as caspase substrates (22), 48 occurred immediately upstream of a glycine residue, and 9 of these proteins received favorable scores for myristoylation and were identified as putative candidates for post-translational myristoylation (Supplemental Table 2).…”

Sorting of lipidated cargo by the Arl2/Arl3 system

“…2 Unlike most Arfs, they are not N-terminally myristoylated even though the glycine residue at position 2 is highly conserved between organisms, but the serine at position 6 important for myristoylation is missing. 3 However they do fit into the Arf subfamily of the Ras superfamily because the structural analysis has shown that both Arl2 and Arl3 display the very dramatic conformational change between the GDP-and the GTP-bound conformations, whereby the first 2 strands of the b-sheet, also called the interswitch toggle, move by 2 residues along the rest of the sheet. 4 Both proteins also have an N-terminal amphiphatic helix characteristic for the Arf subfamily.…”