Integrating the Multiscale Molecular Modelling Techniques in Identification of Rat-TTBK1 Inhibitors from Glycyrrhiza glabra Plant: Homology-Modelling, Docking, MD Simulation, PCA Analysis, Cluster Analysis and MMGB/SA Study

Alzheimer’s disease (AD) is a disturbing mental condition that gradually deteriorates memory and learning capacities. Due to unavailability of effective treatment for AD, there is a tremendous need of newer medication or newer pathways for management of AD. The aim of this study to identify the potential anti-Alzheimer molecule from Glycyrrhiza glabra. Here, an integrated approach combining homology modelling, molecular docking, molecular dynamics (MD) simulation and MMGB/SA was employed for analysing the effectiveness of Glycyrrhiza glabra plant against the rat tau tubulin kinase (ttbk1). Due to absence of any pdb id for rat ttbk1, homology model of rat ttbk1 protein was generated and top scoring model 1 was used for further modelling studies. Amongst the present chemical constituents in targeted plant Isoliquiritin, Glycyrrhizin displayed the good docking score –6.055 and –6.033 kcal/mol respectively. The lower RMSD and RMSF values for Glycyrrhizin-protein and Isoliquiritin-protein complexes suggested about the potential stability of these complexes. The results of MD simulations were further subjected to PCA analysis for better understanding and prediction of obtained in-silico results. The binding energy (dG-bind) for Glycyrrhizin-protein and Isoliquiritin-protein complexes were found to be –95.7035 and –124.2050 kcal/mole indicating the stability of complexes. The obtained results revealed that Isoliquiritin and Glycyrrhizin, present in Glycyrrhiza glabra plant was found to be best scoring molecule and would be further experimentally explored to get a potential therapeutic agent for AD.