Background: Lanosterol synthase (Oxidosqualene cyclase) is an enzyme, which plays a
central role in cholesterol and sterols biosynthesis. Lanosterol synthase drugs are used to lower the level
of cholesterol in the blood and treat wide variety of diseases like atherosclerosis, coronary heart diseases
Objective: There is a great interest in the identification of drugs that target this enzyme for anticholesteraemic
agent using in silico tools.
Methods: Ligand based pharmacophore model was developed using Discovery Studio 2.5. The best
model was used as a tool to retrieve suitable molecule for Lanosterol synthase inhibitor from commercial
database and Virtual screening of large commercially available databases to retrieve the best mole
of Hypo1 using. Molecular docking was done using three different tools named as GOLD, GLIDE and
AUTODOCK 4.0. Density functional theory approach and Density of State spectrum were carried out
using Gaussian 09 and GAUSS SUM 3.0. Contribution of these methods in the selection of anticholesteraemic
compounds has been discussed.
Results: The best pharmacophore model was used to screen the commercial database. Totally 8 compounds
were showed with the best orientation, binding mode and binging energy in the docking analyses.
The orbital energies such as HOMO, LUMO and DOS spectrum for 8 hit compounds showed the
energy gap that results in charge transfer and stability in the active site region. The results showed that
our 8 potent leads could serve for further findings.
Conclusion: In silico approaches, our 8 hit compounds could serve as the better understanding to design
the novel lanosterol synthase inhibitors as anticholesteraemic activity.