IDENTIFICATION OF NOVEL HIGH-AFFINITY CYTOPLASMIC ASPARAGINYL-TRNA SYNTHETASE INHIBITORS USING DOCKING AND MOLECULAR SIMULATION

摘要

Lymphatic filariasis is an endemic disease affecting humans in more than 83 countries, and it is crucial to find drugs to cure this disease. Nearly1.33 billion were at risk of filariasis. In this study, we have targeted Brugia malayi asparaginyl tRNA synthetase (AsnRS) for new drug development againstfilariasis. AsnRS is an essential enzyme for protein synthesis in nematodes and required at various steps of their life cycle. We used computational toolsfor identifying potential molecule which can act as an inhibitor for our target AsnRS. 4133 molecules were selected after screening using Zinc Pharmerand were docked in high throughput manner using vina and top 10% highest scoring molecules were selected. These molecules were re-docked, andonly those molecules were selected which shows less than 2? root-mean-square deviation difference in the top pose predicted by both Autodock4 andAutodock Vina. We identified 11 molecules fitting these criteria which were further subjected to interaction analysis. Molecular dynamics simulationswere performed on molecules showing best interaction based on their binding energy and hydrogen bond formation. It was seen that these moleculeswere bound tightly inside the active site of the receptor. These molecules seem a suitable candidate to undergo in vitro testing.