The small molecular structures of 6 drug
target molecule were retrieved in .sdf format from PubChem as well as NPACT
database and then converted into .pdb format by using viwerlite software(Fig
2). ADME analysis of six compounds predicted about
Adsorption, Distribution, Metabolism and Excretion through SWISS adme software.
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) is
crucial and essential to find out new ligands by virtual screening, carried out
through molecular docking studies. Docking is the process by which two
molecules fit together in 3D space. Here we use Patch dock for molecular docking.
Patch dock works on the basis of shape complementarilyalgorithm and calculates
binding score of ligand with receptor. Molecular docking fits two molecules in
favorable configuration using their topographical features. Practically
molecular docking has been an important technique for the prediction of
protein-ligand interactions and has been used in studies of the structural
basis of biological functions. Binding
interactions of all selected compounds and reference drug is shown in (Fig 3).This is an in-silico study by using
various bioinformatics tools, we have successful docked the 3 D structure of
protein tissue transglutaminase 2 with the natural origin drug targets. Those can be can be potential
drug targets especially nobiletin and curcumin
for inhibition of TG2 and treatment of lung cancer. The combined
approach of ADME and docking used in this work helps in expressing the binding
affinity of drug target in the receptor well and also validates them as
potential candidates for second generation drug target discovery. Development
of increasingly effective and selective inhibitors of Transglutaminase 2 will
make possible elucidation of TG2’s role in a lung cancer, which may ultimately
lead to effective clinical treatments for same. Further in-vitro and in-vivo
studies could be undertaken to prove the same.