Exploring Ketones in Chrysopogon zizanioides: A Computational Molecular Dynamic Approach to c-Met Modulation.

Abstract

Glioblastoma demands the designing of potential drugs as there is no specific treatment available. In this study, we employed computational screening techniques to identify potential modulators of the c-Met receptor from a library of 273 Chrysopogon zizanioides derived compounds which can pass blood brain barrier (BBB) due to their low molecular weight and BBB permeability. Through rigorous molecular docking simulations utilizing Auto Dock Vina plugin integrated with Chimera software, Ketone (C₂₉H₅₆O) (IMPHY012701) emerged as a standout candidate, exhibiting a lower binding energy compared to the reference molecule, AMG 337 which was used as a control compound. The optimal orientation of Ketone (C₂₉H₅₆O) (IMPHY012701) within the c-Met receptor's active site was elucidated, indicating favourable molecular interactions conducive to stable binding. Ketone (C₂₉H₅₆O) (IMPHY012701) shows equilibrium state during 50 ns simulation with least root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values. Notably, Ketone (C₂₉H₅₆O) (IMPHY012701) demonstrated superior binding affinity relative to the control compound, underscoring its potential as a lead for further investigation. This study underscores the utility of computational approaches in drug discovery from natural sources and highlights Ketone (C₂₉H₅₆O) (IMPHY012701) as a promising candidate for the modulation of c-Met-mediated signalling pathways, warranting further experimental validation and exploration of its pharmacological properties.