Apolar burial anchoring of a confined plant glycoside in the gingipain K cleft

Overview This repository contains the computational dataset, raw calculation outputs, parameter files, and supplementary materials supporting the manuscript "Apolar burial anchoring of a confined plant glycoside in the gingipain K cleft". The study evaluates the phytochemical metabolome of Symplocos racemosa against Porphyromonas gingivalis lysine-gingipain (Kgp; PDB: 6I9A) and human monoamine oxidase A (MAO-A; PDB: 2Z5X) aiming to intercept the periodontitis-Alzheimer's disease axis. The data supports the identification of benzoylsalireposide (CID_10369077) as a locally deployable, non-covalent anti-virulence scaffold, characterized by pharmacokinetic confinement (TPSA > 140 Ų) and driven by apolar burial within the Kgp catalytic cleft. Dataset Structure The repository is organized into 7 directories corresponding strictly to the multiscale in silico workflow executed in the study: 01_Biological_Prediction/: Raw prediction spectra from PASS Online and PASS GERO, containing probability-of-activity (Pa) and probability-of-inactivity (Pi) values for the phytochemical library. 02_ADMET/: Raw datasets containing physicochemical, absorption, and toxicity screening results across the evaluated consensus platforms (SwissADME, ADMETlab 3.0, ProTox-3.0, Deep-PK, admetSAR 3.0, ADMET-AI). Includes the compartment assignment matrices. 03_Docking/: Pre-processed receptor structures (.pdb) for Kgp and MAO-A, ligand 3D structures, and raw output docking files including generated binding poses and interaction profiles. 04_MD_and_MMGBSA/: GROMACS (v2023.4) parameter files used to ensure exact reproducibility (run input files .mdp, system topologies .top, and starting coordinates .gro). Also includes the raw end-point free energy decomposition tables (gmx_MMPBSA) for all simulated complexes. Note: Raw, uncompressed 200-ns trajectory files (.xtc/.trr) are excluded due to Zenodo file size limitations (>50 GB/system) but are available from the corresponding authors upon reasonable request. 05_PCA_LDA/: Output datasets containing the Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) clustering metrics (Silhouette, Calinski–Harabasz, Davies–Bouldin) and component loadings for the energy profiles. 06_DFT/: ORCA (v6.1.1) output files (.out) containing pre-optimization, frequency analysis, and single-point evaluations at the B3LYP-D3BJ/def2-TZVP//SMD(water) level. Also includes Multiwfn post-processing outputs for MEP variance and condensed Fukui functions. 07_Network_Pharmacology/: Target prediction datasets, high-confidence STRING protein-protein interaction (PPI) edge-lists, Cytoscape session files (.cys), topological centrality matrices, and raw functional enrichment tables (KEGG, Reactome, GO). Software and Reproducibility Context The data provided herein can be processed or visualized using standard computational biophysics and cheminformatics software: Molecular Dynamics: GROMACS 2023.4 (CHARMM36m / CGenFF) Free Energy Calculations: gmx_MMPBSA v1.6.4 (OBC-II model) Quantum Mechanics: ORCA 6.1.1, Multiwfn 3.8 Network Analysis: Cytoscape 3.10.4 Usage Notes Researchers are free to download, analyze, and repurpose this dataset under the terms of the applied Open Access license (e.g., CC-BY 4.0). If you use this data or the structural hypotheses derived from it, please cite the original manuscript linked to this repository via its DOI.