In silico Screening for Identification of Novel Anti-malarial Inhibitors by Molecular Docking, Pharmacophore Modeling and Virtual Screening.
OBJECTIVE
Drug resistance from affordable drugs has increased the number of deaths from malaria globally. This problem has raised the requirement to design new drugs against multidrug-resistant Plasmodium falciparum parasite.


METHODS
In the current project, we have focused on four important proteins of Plasmodium falciparum and used them as receptors against a dataset of four anti-malarial drugs. In silico analysis of these receptors and ligand dataset was carried out using Autodock 4.2. A pharmacophore model was also established using Ligandscout.


RESULTS
Analysis of docking experiments showed that all ligands bind efficiently to four proteins of Plasmodium falciparum. We have used ligand-based pharmacophore modeling and developed a pharmacophore model that has three hydrophobic regions, two aromatic rings, one hydrogen acceptor and one hydrogen donor. Using this pharmacophore model, we have screened a library of 50,000 compounds. The compounds that shared features of our pharmacophore model and exhibited interactions with the four proteins of our receptors dataset are short-listed.


CONCLUSIONS
As there is a need of more anti-malarial drugs, therefore, this research will be helpful in identifying novel anti-malarial drugs that exhibited bindings with four important proteins of Plasmodium falciparum. The hits obtained in this study can be considered as useful leads in anti-malarial drug discovery.
Sidra
S
Batool
Zeshan Aslam
ZA
Khan
Warda
W
Kamal
Gohar
G
Mushtaq
King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia. prof.makamal@lycos.com.
Mohammad Amjad
MA
Kamal
D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000187:drug effects; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D014584:User-Computer Interface
D000962:Antimalarials; D015800:Protozoan Proteins