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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.




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.