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OJBTM
Online Journal of
Bioinformatics ©
Volume 14 (3): 293-301, 2013
In silico
inhibitors
for
falcipain-3 in Plasmodium
falciparum.
Madhu Sudhana
Saddala, P. Gayathri, J. Obaiah
C. Vallamma and A. Usha Rani*
Dept. of
Zoology, DBT-Bioinformatics Center, Sri Venkateswara University, Tirupati.
ABSTRACT
Saddala
MS, Gayathri
P, Obaiah J,.
Vallamma C. Usha Rani A., In
silico inhibitors for
falcipain-3 in Plasmodium falciparum, Onl
J Bioinform., 14 (3): 293-301,
2013. Inhibition
of falcipain-3 prevents maturation
of Plasmodium
falciparum, suggesting that
the protein could be a target for antimalarial activity.
Falcipain-3 was energy
minimized and subjected to molecular dynamics simulations
using NAMD 2.9
software with CHARMM27 force field in water and the receptor
structure was minimized
with 25,000 steps for 500ps and simulated 10,000 steps for
2ns. 2500 compounds
were screened from PubChem
database through structure
based Virtual screening by referencing Mefloquine.
The screened compounds were docked into the active site of the
protein using Autodock Vina in PyRx
Virtual Screening tool. Results showed that CID3000506,
CID40468067, CID65330, CID40692 and CID4046 had a highest binding
energy of -9.4, -8.9, -8.4,
-7.9 and -7.2 kcal/mol,
respectively. Lead hit compounds were tested for
toxicity and
bioavailability with Osiris and Molinspiration
online
servers. Active site amino acids His18, Asp44, Tyr63, Gln110, Tyr115, Asp168, His196, Glu199,
Gly453 and Met434 could play a role
in binding and catalytic
activity.
KEYWORDS: Falcipain-3,
simulations, docking, PubChem
database, Autodock Vina