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OJBTM
Online
Journal of Bioinformatics ©
Volume 14(2):186-196, 2013
Structure
based virtual screening for DNS methyl transferase-1
inhibitors.
Madhu Sudhana
Saddala, P. Jyothi and A. Usha
Rani
Dept. of Zoology, DBT-Bioinformatics center, Sri Venkateswara
University, Tirupati.
ABSTRACT
Saddala MS, Jyothi
P, Usha
Rani A., Structure based virtual screening for DNS methyl
transferase-1
inhibitors. Onl J Bioinform.,
14(2):186-196,
2013.
DNA methylation alteration is an epigenetic event that can be
induced by
cadmium. Virtual inhibitors for DNA methyltransferase
(DNMT-1) are described. DNMT-1 was energy minimized and
subjected to molecular
dynamic simulations with NAMD 2.9 software and CHARMM27 force
field in water. The
receptor structure was minimized with 25,000 steps for 500 ps
and simulated 100,000 steps for 2ns. 5000 compounds were
screened from the ZINC
database through structure based Virtual screening using Zebularine
as the reference natural drug. The screened compounds were
docked into the
active site of the protein using Autodock
Vina in PyRx .
ZINC00638152, ZINC08426899, ZINC11582506, ZINC15636661,
ZINC22055993
and ZINC25694354 had high binding affinities. Lead
hit compounds were tested
for toxicity and bioavailability using Osiris and Molinspiration
online servers. Active
sites of Lys
162, Asp701, Pro
955, Leu986, Gly1150, Ala1173, Cys1191, Pro1224, Leu1146,
Thy1494, His1502, and
Val1586 appeared to have a role in binding and
catalytic activity.
KEYWORDS: DNMT1,
dynamics, docking, methylation inhibition, Zinc database, Autodock
Vina