In-silico studies on DegP protein of Plasmodium falciparum in search of anti-malarials

J Mol Model. 2016 Sep;22(9):201. doi: 10.1007/s00894-016-3064-3. Epub 2016 Aug 4.


Despite encouraging progress over the past decade, malaria caused by the Plasmodium parasite continues to pose an enormous disease burden and is one of the major global health problems. The extreme challenge in malaria management is the resistance of parasites to traditional monochemotherapies like chloroquine and sulfadoxine-pyrimethamine. No vaccine is yet in sight, and the foregoing effective drugs are also losing ground against the disease due to the resistivity of parasites. New antimalarials with novel mechanisms of action are needed to circumvent existing or emerging drug resistance. DegP protein, secretory in nature has been shown to be involved in regulation of thermo-oxidative stress generated during asexual life cycle of Plasmodium, probably required for survival of parasite in host. Considering the significance of protein, in this study, we have generated a three-dimensional structure of PfDegP followed by validation of the modeled structure using several tools like RAMPAGE, ERRAT, and others. We also performed an in-silico screening of small molecule database against PfDegP using Glide. Furthermore, molecular dynamics simulation of protein and protein-ligand complex was carried out using GROMACS. This study substantiated potential drug-like molecules and provides the scope for development of novel antimalarial drugs.

Keywords: Anti-malarials; DegP protease; Malaria; Molecular dynamics; Secretory protein; Virtual Screening.

MeSH terms

  • Antimalarials / chemistry
  • Computer Simulation*
  • Drug Discovery*
  • Heat-Shock Proteins / chemistry*
  • Models, Molecular*
  • Molecular Dynamics Simulation
  • Periplasmic Proteins / chemistry*
  • Plasmodium falciparum / chemistry*
  • Serine Endopeptidases / chemistry*


  • Antimalarials
  • Heat-Shock Proteins
  • Periplasmic Proteins
  • DegP protease
  • Serine Endopeptidases