title: [Detection of molecular targets on the phosphatidylinositol signaling pathway of Leishmania spp. through bioinformatics tools and mathematical modeling].
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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 .
authors.affiliation: Programa de Estudio y Control de Enfermedades Tropicales-PECET, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Valeria
authors.initials: V
authors.lastname: Velásquez
authors.affiliation: Programa de Estudio y Control de Enfermedades Tropicales-PECET, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ochoa
authors.affiliation: Programa de Estudio y Control de Enfermedades Tropicales-PECET, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Muskus
mesh_terms: D019295:Computational Biology; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008962:Models, Theoretical; D058990:Molecular Targeted Therapy; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D010716:Phosphatidylinositols