QSAR for RNases and theoretic-experimental study of molecular diversity on peptide mass fingerprints of a new Leishmania infantum protein

Humberto González-Díaz, María A. Dea-Ayuela, Lázaro G. Pérez-Montoto, Francisco J. Prado-Prado, Guillermín Agüero-Chapín, Francisco Bolas-Fernández, Roberto I. Vazquez-Padrón, Florencio M. Ubeira

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The toxicity and lowsuccess of current treatments forLeishmaniosis determines the search of newpeptide drugs and/or molecular targets in Leishmania pathogen species (L. infantum and L. major). For example, Ribonucleases (RNases) are enzymes relevant to several biologic processes; then, theoretical and experimental study of the molecular diversity of Peptide Mass Fingerprints (PMFs) of RNases is useful for drug design. This study introduces a methodology that combines QSAR models, 2D-Electrophoresis (2D-E), MALDI-TOF Mass Spectroscopy (MS), BLAST alignment, and Molecular Dynamics (MD) to explore PMFs of RNases. We illustrate this approach by investigating for the first time the PMFs of a new protein of L. infantum. Herewe report and compare new versus old predictive models for RNases based on Topological Indices (TIs) ofMarkov Pseudo-Folding Lattices. These group of indices called Pseudo-folding Lattice 2D-TIs include: Spectral moments π k (x,y), Mean Electrostatic potentials ξk (x,y), and Entropy measures ξk (x,y). The accuracy of the models (training/cross-validation)was as follows: ξk(x,y)-model (96.0%/91.7%) >πk(x,y)-model (84.7/ 83.3) > θk(x,y)-model (66.0/66.7).We also carried out a 2DE analysis of biological samples of L. infantum promastigotes focusing on a 2D-E gel spot of one unknown protein with M < 20, 100 and pI < 7. MASCOT search identified 20 proteins with Mowse score >30, but not one > 52 (threshold value), the higher value of 42 was for a probable DNA-directed RNA polymerase. However, we determined experimentally the sequence of more than 140 peptides. We used QSAR models to predict RNase scores for these peptides and BLAST alignment to confirm some results. We also calculated 3D-folding TIs based on MD experiments and compared 2D versus 3D-TIs on molecular phylogenetic analysis of the molecular diversity of these peptides. This combined strategy may be of interest in drug development or target identification.

Original languageEnglish (US)
Pages (from-to)349-369
Number of pages21
JournalMolecular Diversity
Issue number2
StatePublished - May 2010


  • 2D-Electrophoresis
  • HP Lattice model
  • Leishmania
  • MALDI-TOF mass spectroscopy
  • Markov models
  • Molecular dynamics
  • Protein folding
  • QSAR
  • Ribonucleases
  • Sequence alignment
  • Topological indices

ASJC Scopus subject areas

  • Molecular Biology
  • Drug Discovery
  • Information Systems
  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Catalysis
  • Organic Chemistry


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