Inhibition of Glutathione S Transferase Enzymes by NRF2 Activators: An off-target effect that may limit their therapeutic potential

Inhibition of Glutathione S Transferase Enzymes by NRF2 Activators: An off-target effect that may limit their therapeutic potential

1. Dataset Overview

This repository contains molecular dynamics (MD) simulation analysis data for two systems, designated GST-A1 and GST-A2, investigated in complex with six compounds: acedapsone, demethoxycurcumin, ethacrynic acid, hesperidin, silymarin, and thonningianin. Native/reference systems for both A1 and A2 are also included.

The dataset contains post-simulation analysis outputs used to examine the structural and conformational behaviour of the simulated systems. The analyses include root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen-bond analysis, principal component analysis (PCA), Gibbs free-energy landscape analysis, and binding-energy calculations. Representative structures associated with the conformational analyses are also provided.

The data are organized separately for the A1 and A2 systems, with individual directories for each compound and the corresponding native/reference system.

2. Description of the Dataset Contents

2.1 A1 and A2 directories

The top-level directories, A1 and A2, contain the MD simulation analysis results for the two investigated systems. Each system includes separate directories for the six investigated compounds and a native/reference system.

2.2 Compound-specific directories

Each compound-specific directory contains the analysis data for the corresponding system–compound simulation. The following compounds are represented:

• Acedapsone
• Demethoxycurcumin
• Ethacrynic acid
• Hesperidin
• Silymarin
• Thonningianin

Where applicable, the following categories of files are included.

2.3 Binding-energy files

Files beginning with BE_ contain binding-energy calculation results for the corresponding system and compound.

Format: .txt

2.4 RMSD files

The RMSD files describe structural deviations during the MD simulation.

The dataset includes files corresponding to:

• rmsd_backbone: RMSD of the protein backbone;
• rmsd_comp or rmsd_complex: RMSD of the protein–compound complex;
• rmsd_lig: RMSD of the ligand/compound;
• native RMSD files for the corresponding reference systems.

Format: .xvg

2.5 RMSF files

The RMSF files contain residue-level fluctuation data and are used to examine the relative flexibility of the simulated system during the MD trajectory.

Format: .xvg

2.6 Radius of gyration files

Files beginning with gyrate contain radius of gyration data used to evaluate changes in the overall compactness of the simulated molecular system.

Format: .xvg

2.7 SASA files

Files beginning with sasa contain solvent-accessible surface area data used to examine changes in molecular surface exposure during the simulations.

Format: .xvg

2.8 Hydrogen-bond files

Files beginning with hbond contain hydrogen-bond analysis data for the corresponding system–compound complexes.

Format: .xvg

2.9 PCA files

Files beginning with pca contain principal component analysis data describing the dominant conformational motions sampled during the MD simulations.

Format: .xvg

2.10 Gibbs free-energy files

Files beginning with gibbs contain numerical data associated with Gibbs free-energy landscape analysis of the corresponding simulated systems.

Format: .txt

2.11 Representative structure files

Files named ev1 and ev2 contain representative structures associated with the conformational analyses.

Most representative structures are provided in Protein Data Bank (.pdb) format. The ev1 file for the A2_acedapsone system is provided as a PyMOL session (.pse) file.

3. File Formats

The repository contains the following primary file formats:

• .xvg: numerical MD trajectory analysis data;
• .txt: numerical binding-energy and Gibbs free-energy analysis data;
• .pdb: three-dimensional molecular structure files;
• .pse: PyMOL session file.

4. Data Use and Reuse

This dataset is provided to support the reproducibility and further examination of the molecular dynamics analyses associated with the corresponding research study. The deposited files may be used to evaluate and compare structural stability, molecular flexibility, compactness, solvent exposure, hydrogen-bonding behaviour, conformational motions, free-energy landscapes, and binding-energy results across the investigated systems.