Dataset S1: Tunnel-Mediated Access as a Structural Determinant of Peptide Inhibition Mode — Comprehensive Data Package

This dataset accompanies the manuscript "Tunnel Architecture as a Structural Determinant of Peptide–Enzyme Binding Mode: A Two-Layer Framework Integrating Pocket Enclosure and Channel Geometry across Xanthine Oxidase, Prolyl Endopeptidase, Angiotensin-Converting Enzyme, and Dipeptidyl Peptidase IV" submitted to the Journal of Chemical Information and Modeling. The dataset contains all computational data underlying the two-layer framework for assessing tunnel relevance in enzyme–peptide interactions. The Excel workbook comprises 15 sheets: README — Sheet descriptions and version history Master_Data — Core parameters for four enzymes with fpocket, CAVER, and MD data CAVER_Tunnels — Crystal structure tunnel parameters from CAVER 3.0 fpocket_Pockets — Active-site pocket druggability scores from fpocket Residue_Composition — Tunnel-lining residue composition (hydrophobic, polar, charged) Literature_Survey — 84 enzyme–peptide inhibitor entries (80 unique sequences) with kinetic inhibition types Mutagenesis_Docking — In silico alanine scanning of tunnel-lining residues (4 enzymes × 5 peptides × 3 mutations) Peptide_Diameters — Minimum cross-sectional diameters for 80 food-derived peptides Conformer_Robustness — Extended vs. compact conformer diameter correlation (Spearman ρ = 0.906) Fig3A_PerStructure — Per-structure CAVER and fpocket data CAVER_MD_Dynamics — CAVER 3.0 tunnel dynamics from 100 ns MD trajectories (4 enzymes) CAVER_MD_Cluster1_BR — Per-frame Cluster 1 bottleneck radius values (49 data points) AlaScan_Results — MD-based alanine scanning for XO F914A (gmx_MMPBSA) MD_RMSD_Backbone — Backbone RMSD time courses (1001 points × 4 enzymes, raw + smoothed) MD_RMSD_Summary — Last 20 ns RMSD statistics Software: AutoDock Vina 1.2.5, CAVER 3.0.2, fpocket 4.1, GROMACS 2025.2/2025.3, gmx_MMPBSA 1.6.4, PDBFixer 1.12.0 PDB structures: 3NVY (XO), 3DDU (PEP), 1O86 (ACE), 1X70 (DPP-IV)