Docking, ADMET and Molecular Dynamics Studies of Plant-Based Phenolics as Tumor Pyruvate Kinase M2 Modulators
Rudradip Das, Saumya Kapoor, Moumita Ghosh Chowdhury, Amit Shard · Indian Forester · 2022
The drug discovery is presently threatened by exorbitant costs and is less productive. To challenge the deterioration in the throughput curve, pharmaceutical corporations, and academic scientists are leaning towards plant-based molecules to ascertain new molecules to convert them into pharmacotherapies, and phenolics are the molecules of choice. Natural products, specifically phenolics are undoubtedly explicit sources for development of effective drugs either totally or in a semi-synthetic way and there are numerous examples to support this statement. Molecular docking is chiefly employed to predict novel lead compounds for drug discovery. In this study, phenolics known to act as tumor pyruvate kinase M2 (PKM2) modulators and considered as anticancer agents were subjected to docking studies using Glide and rigorous in silico ADMET studies using the Qikprop suite. In silico investigations were carried out to find out the explicit interactions of the phenolics with PKM2 (PDB IDs 3GR4 and 4B2D) modulators. The docking studies were carried out on phenolics reported as PKM2 modulators. Myricetin was found to be the most suitable anticancer agent for the PKM2 modulation acting on the DASA-binding site with a glide score of -10.746. In addition, the effectiveness of the study was further validated by performing ADMET studies of all the modulators which again established myricetin to be the most favourable one among the selected compounds. It suggested that amongst the “hit list”, myricetin shares the best features to be considered ahead for drug discovery. The results of molecular dynamics simulation studies of myricetin with the DASA-binding pocket of human pyruvate kinase M2 (PDB ID- 3GR4) are strongly in concert with complementary experimental methods discussed above.