N
-Myristoyltransferase (NMT) is a cytosolic monomeric enzyme involved
in the allocation of the myristoyl group to the aminoterminal of glycine
in several viral and eukaryotic cellular proteins. NMT has been validated
as a potential drug target against kinetoplastid for parasitic protozoa.
A multistep virtual screening protocol based on the pharmacophore
modeling, molecular docking, and molecular dynamics simulation was
carried out. Initially, Maybridge database was virtually screened
via a validated pharmacophore model. The effective pharmacophore models
were accompanied with exclusion volumes to improve their receiver
operating characteristic curve to identify potential NMT inhibitors.
The hits identified as actives based on the 3D-pharmacophore model
were evaluated by molecular docking studies. In stepwise screening,
six compounds were shortlisted for the dynamic simulation to get insights
into their binding mode. In conclusion, this study provides fundamental
information about the architecture of the binding site and some crucial
residues that may provide insights into the development of new antiparasitic
agents.