Data supporting the study: Novel EGFR Inhibitors from Phyllanthus niruri Target Resistant T790M Mutations

<p><strong>Dataset Description</strong></p> <p>This repository contains the comprehensive computational dataset supporting the research article <em>"Novel EGFR Inhibitors from Phyllanthus niruri Target Resistant T790M Mutations"</em>. This study addresses the critical challenge of acquired drug resistance in Hepatocellular Carcinoma (HCC) mediated by the EGFR T790M "gatekeeper" mutation.</p> <p>The dataset provides raw inputs, configuration files, and quantitative analysis outputs for a library of 37 phytochemicals derived from <em>Phyllanthus niruri</em>, compared against clinical standards (Osimertinib and Mobocertinib). The study identifies dual-mechanism inhibitors capable of "super-polar anchoring" or "hydrophobic packing" to overcome resistance, combined with intrinsic hepatoprotective profiles suitable for cirrhotic populations.</p> <p><strong>Methodological Pipeline</strong></p> <p>The data was generated using a high-throughput <em>in silico</em> pipeline including:</p> <ul> <li><strong>Structural Preparation:</strong> Refinement of the EGFR T790M/V948R kinase domain (PDB ID: 7A6K).</li> <li><strong>ADMET Profiling:</strong> Pharmacokinetics, toxicity (hERG, DILI), and biological activity predictions using SwissADME, pkCSM, Deep-PK, and PASS Online.</li> <li><strong>Molecular Docking:</strong> Blind docking campaigns performed with SwissDock (Attracting Cavities 2.0).</li> <li><strong>Molecular Dynamics:</strong> 100-nanosecond all-atom simulations executed in GROMACS 2023.4 (CHARMM36m force field).</li> <li><strong>Thermodynamics:</strong> Binding free energy calculations via the MM-PBSA method.</li> </ul> <p><strong>Repository Structure</strong></p> <p>The dataset is organized into four (4) primary directories:</p> <ul> <li><strong>01_Protein_Preparation:</strong> Contains the cleaned, protonated, and validated receptor structure used for grid generation.</li> <li><strong>02_ADMET_Bioactivity_Predictions:</strong> Consists of 39 individual Excel workbooks containing detailed PK/Tox and kinome profiling for each compound.</li> <li><strong>03_Molecular_Docking:</strong> Includes raw output files, clustered binding poses, and summary energy scores (Delta G).</li> <li><strong>04_Molecular_Dynamics_Results:</strong> Contains statistical analysis reports (.txt) and high-resolution plots (.png) for RMSD, RMSF, Radius of Gyration, Hydrogen Bonds, and MM-PBSA energies. <em>Note: Raw trajectories are excluded due to size limitations.</em></li> </ul> <p><strong>Usage Notes</strong></p> <p>This dataset is intended to ensure the reproducibility of the <em>in silico</em> findings and to foster further research into natural product-based kinase inhibitors. Users can utilize the docked poses and topology files to extend simulation times or apply alternative scoring functions.</p>