Prediction of N-myristoylation modification of proteins by SVM

Abstract

Attachment of a myristoyl group to NH2-terminus of a nascent protein among protein post-translational modification (PTM) is called myristoylation. The myristate moiety of proteins plays an important role for their biological functions, such as regulation of membrane binding (HIV-1 Gag) and enzyme activity (AMPK). Several predictors based on protein sequences alone are hitherto proposed. However, they produce a great number of false positive and false negative predictions; or they cannot be used for general purpose (i.e., taxon-specific); or threshold values of the decision rule of predictors need to be selected with cautiousness. Here, we present novel and taxon-free predictors based on protein primary structure. To identify myristoylated proteins accurately, we employ a widely used machinelearning algorithm, support vector machine (SVM). A series of SVM predictors are developed in the present study where various scales representing physicochemical and biological properties of amino acids (from the AAindex database) are used for numerical transformation of protein sequences. Of the predictors, the top ten achieve accuracies of >98% (the average value is 98.34%), and also the area under the ROC curve (AUC) values of >0.98. Compared with those of previous studies, the prediction accuracies are improved by about 3 to 4%.

Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role

“…The G residue at the first position is necessary for this PMT, while at the second position there is preferentially an uncharged residue (except for proline (P)) or an aromatic amino acid. At the fifth position, uncharged residues are found, preferentially serine (S) and threonine (T) (for a review see [ 33 ]), while P is not accepted at the sixth position [ 34 ]. In sum, three regions finely regulate myristoylation: the binding pocket (positions from 1 to 6), the catalytic domain (positions from 7 to 10) and the hydrophilic linker (position from 11 to 17) [ 34 , 35 ] ( Figure 2 a).…”

“… Protein sequence required for myristoylation and sequences of retroviral myristoylated MA domains. ( a ) Pro-myristoylated consensus sequence underlying the three regions regulating myristoylation: the binding pocket (positions 1–6), the catalytic domain (positions 7–10) and the hydrophilic linker (positions 11–17) [ 34 , 35 ]. ( b ) Comparison of the first 17 residues of myristoylated MA domains in different retroviruses.…”