3D entropy and moments prediction of enzyme classes and experimental-theoretic study of peptide fingerprints in Leishmania parasites.

The number of protein 3D structures without function annotation in Protein Data Bank (PDB) has been steadily increased. This fact has led in turn to an increment of demand for theoretical models to give a quick characterization of these proteins. In this work, we present a new and fast Markov chain model (MCM) to predict the enzyme classification (EC) number. We used both linear discriminant analysis (LDA) and/or artificial neural networks (ANN) in order to compare linear vs. non-linear classifiers. The LDA model found is very simple (three variables) and at the same time is able to predict the first EC number with an overall accuracy of 79% for a data set of 4755 proteins (859 enzymes and 3896 non-enzymes) divided into both training and external validation series. In addition, the best non-linear ANN model is notably more complex but has an overall accuracy of 98.85%. It is important to emphasize that this method may help us to predict not only new enzyme proteins but also to select peptide candidates found on the peptide mass fingerprints (PMFs) of new proteins that may improve enzyme activity. In order to illustrate the use of the model in this regard, we first report the 2D electrophoresis (2DE) and MADLI-TOF mass spectra characterization of the PMF of a new possible malate dehydrogenase sequence from Leishmania infantum. Next, we used the models to predict the contribution to a specific enzyme action of 30 peptides found in the PMF of the new protein. We implemented the present model in a server at portal Bio-AIMS (http://miaja.tic.udc.es/Bio-AIMS/EnzClassPred.php). This free on-line tool is based on PHP/HTML/Python and MARCH-INSIDE routines. This combined strategy may be used to identify and predict peptides of prokaryote and eukaryote parasites and their hosts as well as other superior organisms, which may be of interest in drug development or target identification.

Review of MARCH-INSIDE & complex networks prediction of drugs: ADMET, anti-parasite activity, metabolizing enzymes and cardiotoxicity proteome biomarkers.

In this communication we carry out an in-depth review of a very versatile QSPR-like method. The method name is MARCH-INSIDE (MARkov CHains Ivariants for Network Selection and DEsign) and is a simple but efficient computational approach to the study of QSPR-like problems in biomedical sciences. The method uses the theory of Markov Chains to generate parameters that numerically describe the structure of a system. This approach generates two principal types of parameters Stochastic Topological Indices (sto-TIs). The use of these parameters allows the rapid collection, annotation, retrieval, comparison and mining structures of molecular, macromolecular, supramolecular, and non-molecular systems within large databases. Here, we review and comment by the first time on the several applications of MARCH-INSIDE to predict drugs ADMET, Activity, Metabolizing Enzymes, and Toxico-Proteomics biomarkers discovery. The MARCH-INSIDE models reviewed are: a) drug-tissue distribution profiles, b) assembling drug-tissue complex networks, c) multi-target models for anti-parasite/anti-microbial activity, c) assembling drug-target networks, d) drug toxicity and side effects, e) web-server for drug metabolizing enzymes, f) models in drugs toxico-proteomics. We close the review with some legal remarks related to the use of this class of QSPR-like models.