Now showing 1 - 3 of 3
  • Publication
    Computational selection of novel antigenic targets in the Mycobacterium bovis proteome
    The discovery of novel antigens is an essential requirement in devising new diagnostics for use in both M. tuberculosis (Mtb) and M. bovis control programmes. Reverse vaccinology is now a feasible method of extracting potential immunogenic epitopes from bacterial genomes to reduce the cost of experimental screening of antigens for anamnestic responses in infected hosts. Since a significant focus has been on the role of CD4+ T cells, the ability to predict peptide binding to MHC-II molecules is seen as a key step in discovery.Previous antigen-mining experiments for identification of novel diagnostic or vaccine candidates for human and bovine TB follow a targeted approach, where specific groups of proteins suspected to contain likely candidates are identified and evaluated for  mmunogenicity. A disadvantage of those approaches is that they are restricted to a relatively small set of proteins biased by the initial selection criteria. Our objective was to computationally select antigens in a less biased manner.
      147
  • Publication
    CycloPs : generating virtual libraries of cyclized and constrained peptides including nonnatural amino acids
    We introduce CycloPs, software for the generation of virtual libraries of constrained peptides including natural and nonnatural commercially available amino acids. The software is written in the cross-platform Python programming language, and features include generating virtual libraries in one-dimensional SMILES and three-dimensional SDF formats, suitable for virtual screening. The stand-alone software is capable of filtering the virtual libraries using empirical measurements, including peptide synthesizability by standard peptide synthesis techniques, stability, and the druglike properties of the peptide. The software and accompanying Web interface is designed to enable the rapid generation of large, structurally diverse, synthesizable virtual libraries of constrained peptides quickly and conveniently, for use in virtual screening experiments. The stand-alone software, and the Web interface for evaluating these empirical properties of a single peptide, are available at http://bioware.ucd.ie.
      2450Scopus© Citations 30
  • Publication
    Design and Evaluation of Antimalarial Peptides Derived from Prediction of Short Linear Motifs in Proteins Related to Erythrocyte Invasion
    The purpose of this study was to investigate the blood stage of the malaria causing parasite, Plasmodium falciparum, to predict potential protein interactions between the parasite merozoite and the host erythrocyte and design peptides that could interrupt these predicted interactions. We screened the P. falciparum and human proteomes for computationally predicted short linear motifs (SLiMs) in cytoplasmic portions of transmembrane proteins that could play roles in the invasion of the erythrocyte by the merozoite, an essential step in malarial pathogenesis. We tested thirteen peptides predicted to contain SLiMs, twelve of them palmitoylated to enhance membrane targeting, and found three that blocked parasite growth in culture by inhibiting the initiation of new infections in erythrocytes. Scrambled peptides for two of the most promising peptides suggested that their activity may be reflective of amino acid properties, in particular, positive charge. However, one peptide showed effects which were stronger than those of scrambled peptides. This was derived from human red blood cell glycophorin-B. We concluded that proteome-wide computational screening of the intracellular regions of both host and pathogen adhesion proteins provides potential lead peptides for the development of anti-malarial compounds.
      198Scopus© Citations 5