TITLE:
Molecular Docking Investigation of New Inhibitors of Falciparum vivax
AUTHORS:
Kassim Adebambo, Sinthusan Gunaratnam
KEYWORDS:
Falciparum vivax, Hydrogen Bond Interaction, Molecular Docking, Lipinski’s Rule, N-Myristoyltransferase (PvNMT)
JOURNAL NAME:
Computational Molecular Bioscience,
Vol.8 No.2,
June
7,
2018
ABSTRACT: Despite the vigorous research and development, as of
2017, there is currently no widely available antimalarial vaccine. An effective,
commercially available vaccine would be a huge game changer; however, it seems
like there is still a long way to go until that target is reached. Therefore,
the purpose of this study was to use molecular docking technique to identify
new inhibitors for a novel antimalarial target with the overall aim of finding
hit compounds which could be further optimized to become potential drug
candidates. The docking protocol AutoDockVina was used alongside the molecular
visualisation software UCSF Chimera to dock 100 naphthoquinones (labelled
TM1-100) and 66 aryl diketones (labelled TM101-166) with the chosen target, Plasmodium vivax N-myristoyltransferase
(PvNMT). Each docking session yielded
the best 9 binding modes between the ligand and target. The hydrogen bond
interactions of all binding modes were analysed, and the top six target
molecules (TM) were short listed as the possible hit compounds (TM40, TM65,
TM66, TM81, TM94 and TM165). These compounds displayed more than six hydrogen
bonds under 3 angstroms over the 9 binding modes. Using Lipinski’s rule of 5,
the potential hit compounds were further analysed to determine the
drug-likeness and all were found to obey the parameters. Following the same
method used to dock the ligands, twelve FDA approved antimalarial drugs were
also docked with PvNMT for comparison
purposes. Apart from proguanil, the other eleven antimalarial drugs displayed
fewer hydrogen bonds under 3 angstroms over the 9 binding modes compared to all
six of the potential hit compounds. This study discovered six compounds which
displayed stronger interactions with the target protein compared to majority of
the FDA approved drugs. The results of this investigation gave us new molecules
that could be further investigated for the designing of novel drug-like
compounds for the treatment of Malaria.