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

in Molecular biotechnology by Somayeh Sabaghan, Rashi Srivastava, Pardeep Yadav, Muskan Kumari, Renuka Soni, Shanuja Beri, Saurabh Kumar Jha

TLDR

  • Computational screening identifies Ketone (CHO) (IMPHY012701) as a promising candidate for modulating c-Met receptor in glioblastoma treatment.

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 (CHO) (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 (CHO) (IMPHY012701) within the c-Met receptor's active site was elucidated, indicating favourable molecular interactions conducive to stable binding. Ketone (CHO) (IMPHY012701) shows equilibrium state during 50 ns simulation with least root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values. Notably, Ketone (CHO) (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 (CHO) (IMPHY012701) as a promising candidate for the modulation of c-Met-mediated signalling pathways, warranting further experimental validation and exploration of its pharmacological properties.

Overview

  • Study Focus: Computational screening of Chrysopogon zizanioides-derived compounds to identify potential modulators of the c-Met receptor.
  • Hypothesis: The design of potential drugs for glioblastoma treatment through molecular docking simulations using computational screening techniques.
  • Primary Objective: To identify a lead compound that can pass the blood brain barrier and exhibit binding affinity to the c-Met receptor.

Comparative Analysis & Findings

  • Ketone (CHO) (IMPHY012701) emerged as a standout candidate with lower binding energy compared to the reference molecule, AMG 337.
  • Optimal orientation of Ketone (CHO) (IMPHY012701) within the c-Met receptor's active site indicates favourable molecular interactions for stable binding.
  • Superior binding affinity of Ketone (CHO) (IMPHY012701) relative to the control compound suggests its potential as a lead for further investigation.

Implications and Future Directions

  • This study highlights the utility of computational approaches in drug discovery from natural sources.
  • Ketone (CHO) (IMPHY012701) warrants further experimental validation and exploration of its pharmacological properties.
  • Future research directions include the investigation of Ketone (CHO) (IMPHY012701)'s effects on c-Met-mediated signaling pathways in glioblastoma treatment.
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