Summary of - Molecular docking and dynamics guided approach to identify potential anti-inflammatory molecules as NRF2 activator to protect against drug-induced liver injury (DILI): a computational study

Document Type

Article

Abstract

Study background: The research presented titles “Molecular docking and dynamics guided approach to identify potential anti-inflammatory molecules as NRF2 activator to protect against drug-induced liver injury (DILI): a computational study” by Ajay Mili, Shubham Das, Dr Krishnadas Nandakumar and Dr Richard Lobo centered on identification of anti-inflammatory molecules as activator of NRF2 pathway using the computational method.

Research Goal and Hypothesis: The primary goal is to identify anti-inflammatory molecules as activator of NRF2 pathway.

Methodological Approach: Acquiring and preparing the KEAP1-NRF2 Protein (PDB: 4L7D) with Schrodinger Suite was followed by developing a ligand library (Anti-inflammatory library downloaded from ChemDiv database). Molecular docking studies were performed in HTVS, SP, and XP modes, respectively. Based on the docking score, interaction, ADMET and binding free energy, the top ten compounds were selected and subjected to induced-fit docking (IFD) analysis for further study. The top three molecules were chosen for a molecular dynamics (MD) simulation study. Using the Desmond module of the Schrodinger Suite, the stability of the protein-ligand complex and protein-ligand contact throughout 100ns were evaluated during the MD simulation study.

Result and discoveries:

1: Three compounds (23013, 12895 and 9866) demonstrated exceptional stability and consistently maintained essential interactions throughout the study.

2: These compounds are anticipated to act as effective NRF2 activators.

3: Further in vitro and in vivo assessments are required to confirm their potential.

4: The anticipated outcome of future research is to determine if these compounds can prevent drug-induced liver injury (DILI) through NRF2 activation, supporting future drug development.

Citation to the base paper: Ajay Mili, Subham Das, Krishnadas Nandakumar & Richard Lobo (2023) Molecular docking and dynamics guided approach to identify potential anti-inflammatory molecules as NRF2 activator to protect against drug-induced liver injury (DILI): a computational study, Journal of Biomolecular Structure and Dynamics, 41:19, 9193-9210, DOI: 10.1080/07391102.2022.2141885.

Publication Date

2023

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