Computer- Aided Drug Discovery

Malaria parasites include five plasmodium species specifically Plasmodium falciparum, P.vivax, P.ovale, P. malariae P. knowlesi which are present in the Philippines. Recently, there is a growing resistance to anti-malarial drugs hence the need for the development of new therapeutics against malaria. Plasmodium falciparum Signal Peptide Peptidase (PfSPP) is a conserved protein sequence in all five species and served as drug target. Three-dimensional structure of PfSPP was generated via homology modelling and was used to generate a pharmacophore model, which was subsequently used to screen over 170,000 library compounds. At the end of the work, 3 compound leads were found bind better than a known drug which renders them as lead compounds. The high-scoring compounds were docked to the target enzyme and the high affinity hits were further developed in silico using De Novo Evolution technique. After which, lead compounds further increased their binding to the active site. This work served as my undergraduate thesis and was selected as one of the best biochemistry thesis in 2012.