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Biomédica

Print version ISSN 0120-4157

Abstract

VELASQUEZ; OCHOA, Rodrigo  and  MUSKUS, Carlos. Detection of molecular targets on the phosphatidylinositol signaling pathway of Leishmania spp. through bioinformatics tools and mathematical modeling. Biomédica [online]. 2015, vol.35, n.2, pp.235-246. ISSN 0120-4157.  http://dx.doi.org/10.7705/biomedica.v35i2.2298.

Introduction: Leishmaniasis is a disease of high impact on public health. Research on drugs for its treatment is considered a priority by the World Health Organization. The phosphatidyl-inositol signaling pathway is interesting to explore because it is involved in the survival of the parasite, by controlling osmoregulation, transport through membranes, and activation of transcription factors. Objective: To propose drug targets against the disease through bioinformatic analysis and mathematical modeling of this signaling pathway. Materials and methods: The phosphatidyl-inositol pathway proteins were characterized through Pfam and TriTrypDB databases. Subsequently, a similarity analysis with human proteins was performed using the OrthoMCL and InParanoid7 tools. Finally, a boolean model of the pathway was proposed using PROMOT and CellNetAnalyzer softwares. Results: The phosphatidyl-inositol signaling pathway in Leishmania spp. was reconstructed and described. The similarity analysis determined the feasibility of the phosphatidyl-inositol pathway proteins as molecular targets. Mathematical models allowed integrating the elements of the path and predicted an inhibitor effect. The following were proposed as drug targets: inositol-3-phosphate-5-phosphatase, phosphatidylinositol-4-kinase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and Inositol-1P-polyphosphate phosphatase. Conclusion: The phosphatidyl-inositol signaling pathway is robust from the point of view of the qualitative model and the proteins found. Thus, potential drug targets against leishmaniasis were identified. Subsequently we will seek to detect drugs against this set of proteins and validate them experimentally .

Keywords : leishmaniasis [terapia]; leishmaniasis [therapy]; phosphatidylinositols; computational biology; mathematical models.

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