Harmaline–NaV1.7 DFT and Docking Dataset

This repository contains the computational data and final analysis scripts supporting the study “Quantum-Chemical and Structure-Guided Analysis of Harmaline Recognition at Human NaV1.7.” The study combines density functional theory (DFT) calculations with structure-guided molecular docking to investigate the molecular properties of harmaline and its structural compatibility with the experimentally defined intracellular antagonist-binding region (site BIG) of human NaV1.7. The dataset includes raw and processed data for neutral and protonated harmaline (HARM0 and HARMH), neutral and protonated harmine (HME0 and HMEH), and neutral ranolazine (RAN0). Ranolazine was included in the quantum-chemical analyses as a pharmacological reference but was not included in the production docking matrix. Quantum-chemical calculations were performed at the ωB97X-D/def2-TZVP level using the SMD implicit-water model. The repository contains Gaussian input and output files, optimized molecular structures, frequency and thermochemical data, dipole moments, and frontier molecular orbital descriptors. Structure-guided docking was performed using experimentally determined human NaV1.7 cryo-EM structures PDB 8I5B, 8S9B, and 8S9C. The production docking dataset comprises a complete 3 receptor × 4 ligand matrix using HARMH, HARM0, HMEH, and HME0. The repository contains prepared receptor inputs, docking-score summaries, residue-contact analyses, native-site correspondence metrics, pose-occupancy data, native-ligand redocking results, and cross-receptor consensus analyses. Protein–ligand interaction fingerprints generated using the final ProLIF implicit-hydrogen workflow are also included, together with the final scripts used for receptor preparation, ligand preparation, redocking assessment, docking-matrix analysis, pose-occupancy analysis, native-site overlap analysis, and interaction-fingerprint analysis. The docking results are intended to assess structural compatibility with the experimentally established site-BIG region rather than to define a unique experimentally validated binding pose. AutoDock Vina scores should therefore be interpreted as comparative docking scores and not as experimental binding free energies, dissociation constants, or predicted IC50 values. The repository also includes Supporting Information tables, dataset metadata, a file inventory, and SHA-256 checksums for integrity verification. Developmental, unsuccessful, debugging, and superseded analysis scripts were excluded from the final repository package. Original human NaV1.7 structural coordinates should be obtained from the Protein Data Bank entries 8I5B, 8S9B, and 8S9C and cited together with the corresponding structural publication.