Abstract

Animals and higher plants express endogenous peptide antibiotics called defensins. These small cysteine-rich peptides are active against bacteria, fungi and viruses. Plectasin—the first defensin has been isolated from a fungus, the saprophytic ascomycetePseudoplectania nigrella. Polypeptides having antimicrobial activity may be capable of reducing the number of living cells of Bacillus subtilis (ATCC 6633). Plectasin has primary, secondary and tertiary structures that closely resemble those of defensins found in spiders, scorpions, dragonflies and mussels. Recombinant plectasin was produced at a very high, and commercially viable, yield and purity. In vitro, the recombinant peptide was especially active againstStreptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin showed extremely low toxicity in mice, and cured them of experimental peritonitis and pneumonia caused by S. pneumoniae as efficaciously as vancomycin and penicillin. These findings identify fungi as a novel source of antimicrobial defensins, and show the therapeutic potential of plectasin. They also suggest that the defensins of insects, molluscs and fungi arose from a common ancestral gene. The Poisson-Boltzmann equation models the electrostatic potential generated by fixed charges on a polarizable solute immersed in an ionic solution. This approach is often used in computational structural biology to estimate the electrostatic energetic component of the assembly of molecular biological systems. In the last decades, the amount of data concerning proteins and other biological macromolecules has remarkably increased. To fruitfully exploit these data, a huge computational power is needed as well as software tools capable of exploiting it. It is therefore necessary to move towards high performance computing and to develop parallel implementations of already existing and of novel algorithms. In this Research and Scientific Project, we propose the implementation of a full Poisson-Boltzmann solver based on a finite-difference scheme using different and combined parallel schemes and in particular a mixed MPI-CUDA implementation. Here, we have for the first time discovered a A Rational predicted pDRS-18-plectasin peptide-mimetic pharmacophore comprising antibiotic properties with therapeutic potential from a saprophytic fungus using BiogenetoligandorolTM drug discovery process combined MPI-CUDA parallel solution of linear and nonlinear Poisson-Boltzmann equation.