Thumbnail Image

Theses

Browse

20181
Reset filters
Subject: Bioinformatics × Author: Naina Kumari × End date: 2019 ×
Reset filters

Search Results

Now showing 1 - 1 of 1
  • Thumbnail Image
    ThesisItemOpen Access
    Virtual high throughput screening of sodium channel blockers as potential insecticide leads
    (CCSHAU, 2018) Naina Kumari; Sudhir Kumar
    Sodium channels are integral transmembrane proteins responsible for the initiation and propagation of action potential. Sodium channel consists of α and β subunits. α subunit is responsible for voltage dependent ion conductance whereas β subunit is responsible for membrane localization. By the use of virtual high throughput screening (molecular docking), potential inhibitors of voltage gated sodium channel were identified. vHTS is a computational method for screening in silico collection of compound libraries. Using vHTS, the binding affinity of the compounds from in silico library and target receptor was predicted. The crystal structure of insect sodium channel (5X0M) consisting of 1553 amino acids was retrieved from RCSB PDB and the active site and binding pocket were identified by CastP tool.. On the basis of substructure similarity of well-known inhibitors of sodium channel, 2,06,404 small molecules/ligands were obtained from ZINC15 database. Out of 2, 06,404 ligands, 1,65,437 were selected on the basis of Lipinski’s rule of 5. Molecular docking of the ligands with the sodium channel protein was performed using USCF DOCK6. 4,854 Docked ligands were obtained on the basis of acceptable binding energy score. The ligands were further filtered by their ADMET properties prediction through vNN-ADMET and TEST. Out of 2,06,404 ligands, 47 ligands were identified as non-toxicant and potential insect sodium channel blockers. The interaction study of the 47 accepted leads with the sodium channel protein revealed that ARG 1138, ARG 1120, GLU 1435, LEU 1224, ILE 1152, ASP 1412, GLU 1123, LEU 1224 and TYR 1430 are the key residues involved in interaction through hydrogen bonding, electrostatic interactions or vander waals forces.