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OJBTM
Online Journal of Bioinformatics©
Volume 22 (2):
96-102, 2021.
Structure based
virtual screening for DNA methyl transferase-1 inhibitors.
Madhu Sudhana Saddala, P. Jyothi and A. Usha
Rani
Dept. of Zoology,
DBT-Bioinformatics Center, Sri Venkateswara University,
Tirupati-517502.
ABSTRACT
Saddala MS, Jyothi P,
Rani AU., Structure based virtual screening for DNA methyl transferase-1
inhibitors, Onl J Bioinform.,
22 (2): 96-102, 2021. Cadmium (Cd), a human carcinogen likely acts via epigenetic DNA
methylation (MeTase). DNA methyltransferases (DNMTs) epigenetic
enzymes could inhibit cancer. We describe computational methods to identify and
optimize DNMT’s.
DNMT-1 was energy minimized subjected to molecular dynamics simulations with
NAMD software and CHARMM27 force field in water and receptor structure minimized
25,000 steps for 500 ps and simulated 10,00000 steps
for 2ns. We screened 5000 compounds in ZINC database by virtual screening natural
drug Zebularine. These were docked into the active
site of protein with Autodock Vina
in PyRx Virtual Screening tool. We generated ZINC00638152, ZINC08426899, ZINC11582506, ZINC15636661, ZINC22055993 and
ZINC25694354 with high binding affinities. We evaluated
these for toxicity and bioavailability on Osiris and Molinspiration
online servers. Active amino acid Lys 162, Asp701, Pro 955, Leu986, Gly1150, Ala1173, Cys1191,
Pro1224, Leu1146, Thy1494, His1502, and Val1586 were found to be
involved in binding and catalytic activity.
Keywords: DNMT1, dynamics, docking, methylation inhibition, Zinc
database, Autodock Vina.
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