An in-silico drug forage against trmd gene of salmonella typhimurium (LT2)

Abstract

Salmonella, that is multidrug resistant (MDR) poses a serious threat to people. An essential enzyme needed for cell growth and survival, TrmD is an S-adenosyl methionine (AdoMet or SAM)dependent methyl transferase that creates themethylationm1G37 in tRNA pro. It is distinct from its eukaryotic and archeal cousin Trm5. In-vitro tests of the effectiveness of Actinomycetes against Salmonella Typhimurium, homology modeling of the target protein, molecular docking, predictions of the ADME/T properties of particular antibacterial molecules, research into the druglikeness of particular ligands, and computational quantum mechanical modeling of particular hits are all objectives of this study. In order to comprehend the inhibitory mechanism and the spatial orientation of the ligands, as well as to identify important amino acid residues within the substrate-binding pocket that can be used for structure-based drug design, the study offers an insight into biomolecular interactions. The target protein (modeled using MODELLER) of Salmonella Typhimurium (LT2) was docked with a variety of natural products, kinase inhibitors, nucleoside mimics, and indole derivatives. After the compounds were narrowed, the compounds that were able to be effective against target protein and bind with the amino acid L138 in the active site were found to be one Natural Products; Antineoplaston, five kinase inhibitors 2-(4Fluorophenyl)-N-[2-(1H-indol-3-yl)ethyl] acetamide; N-benzyl-2-(2-methyl-1H-indol-3-yl)acetamide; 1-(1,3-Dimethylpyrazol-4-yl)-3-[(2R)-1-hydroxy-3-phenylpropan-2-yl]urea; ; 1-[(2S)-1Hydroxy-3-phenylpropan-2-yl]-3-(1-pyridin-4-ylethyl)urea;1-(1,5-Dimethylpyrazol-3-yl)-3-[(2S)1-hydroxy-3-phenylpropan-2-yl]urea three indole derivative (N-[(3,4-dimethoxyphenyl)methyl]3-(1H-indol-6-yl)propenamide;N-[2-(6-methoxy-1H-indol-3-yl)ethyl]-3-phenylpropanamide and2-(4-fluorophenyl)-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide. Similarly, two nucleosidemimetics 7-[(3R)-1-Benzoylpyrrolidin-3-yl]-N-methylthieno[2,3-b] pyrazine-6-carboxamide and[3-(2-Methylpropyl)-1,2-oxazol-5-yl]-[(3S)-3-(1H-pyrazolo[3,4-b] pyridin-6-yl) piperidin-1-yl]methanone were found to be effective. Natural Product Antineoplaston's DFT calculation revealed that the substance was a stable and reactive molecule with drug-like properties. Keywords: ADMET, trmD, homology modelling, drug discovery, molecular docking, therapeutic alternative.