The small molecular structures of 6 drugtarget molecule were retrieved in .sdf format from PubChem as well as NPACTdatabase and then converted into .pdb format by using viwerlite software(Fig2). ADME analysis of six compounds predicted aboutAdsorption, Distribution, Metabolism and Excretion through SWISS adme software.All compounds passes Lipinski rule of five.There is zero violation of rule shown by these molecules shown in (Table 2).
Hence these results may be used for generation of new drug targets against TG2.Structure based drug designing (SBDD) iscrucial and essential to find out new ligands by virtual screening, carried outthrough molecular docking studies. Docking is the process by which twomolecules fit together in 3D space. Here we use Patch dock for molecular docking.
Patch dock works on the basis of shape complementarilyalgorithm and calculatesbinding score of ligand with receptor. Molecular docking fits two molecules infavorable configuration using their topographical features. Practicallymolecular docking has been an important technique for the prediction ofprotein-ligand interactions and has been used in studies of the structuralbasis of biological functions. Bindinginteractions of all selected compounds and reference drug is shown in (Fig 3).This is an in-silico study by usingvarious bioinformatics tools, we have successful docked the 3 D structure ofprotein tissue transglutaminase 2 with the natural origin drug targets. Those can be can be potentialdrug targets especially nobiletin and curcumin for inhibition of TG2 and treatment of lung cancer.
The combinedapproach of ADME and docking used in this work helps in expressing the bindingaffinity of drug target in the receptor well and also validates them aspotential candidates for second generation drug target discovery. Developmentof increasingly effective and selective inhibitors of Transglutaminase 2 willmake possible elucidation of TG2’s role in a lung cancer, which may ultimatelylead to effective clinical treatments for same. Further in-vitro and in-vivostudies could be undertaken to prove the same.