Umbelliferone as a DR5-TRAIL interfacial stabilizer: staged oligomer-state docking and a fluorescence binding assay

Published: 10 November 2026| Version 3 | DOI: 10.17632/2s898j5dk7.3
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Description

This dataset contains the computational and experimental data underlying the study “Umbelliferone Enhances TRAIL-DR5 Binding in vitro at Micromolar Concentrations: a Mechanism Resolved by Staged Oligomer-State Interaction Profiling,” submitted to the Indonesian Journal of Chemistry. It lets readers reproduce the docking rankings, the interaction analysis, and the binding-assay results reported in the article and its supplementary material. The deposit is organised in four folders, accompanied by the supplementary material document (Methods S1, Text S1, Tables S1 to S8, and Figures S1 and S2). Docked structures: the four rigid-body poses of coumarin, ellagic acid, gallic acid, and umbelliferone at the dimeric DR5-TRAIL-DR5 interface, generated with Hex 8.0.0 from PDB entry 1D4V (COU_dimer_clean.pdb, EA_dimer_clean.pdb, GA_dimer_clean.pdb, UMB_dimer_clean.pdb). In every file, chains A and C are DR5 (residues 69 to 185), chain B is TRAIL (residues 119 to 281), and chain X is the docked ligand, written as UNK 1. Because residues 119 to 185 occur in both proteins under this numbering, contacts in that range must be assigned from the chain identifier, not the residue number. Interaction analysis: a workbook with Hex E-values for all fifteen compounds at the monomeric and dimeric states, the ranking sheet, and the per-compound BIOVIA Discovery Studio contact listings. These listings are unfiltered and include the chain-terminus contacts excluded from the article. Binding assay: the unmodified GloMax reader export (3 June 2026) behind the dose-response data. Vina cross-check: the AutoDock Vina versus Hex comparison table. Vina was run as a single job per ligand with no fixed random seed, so the scores are not bit-reproducible. A README in the archive root repeats this layout and the reuse caveats. The data are shared under a CC BY 4.0 licence.

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Steps to reproduce

COMPUTATIONAL WORKFLOW Structures: the fifteen candidate compounds were retrieved from PubChem as SDF files, and the DR5-TRAIL complex was taken from RCSB PDB entry 1D4V. Ligands were energy-minimised with the Minimize Structure module of UCSF Chimera 1.11.2 and converted from SDF to PDB. The complex was split into chain A (DR5) and chain B (TRAIL), each chain minimised in Chimera; crystallographic ligands and waters were removed and geometry was checked with MolProbity. Staged docking: each compound was docked with Hex 8.0.0 (rigid-body FFT correlation; Shape, Electro and DARS terms) against three states in turn, the monomer (DR5-TRAIL), the dimer (DR5-1-TRAIL-DR5-2) and the trimer (DR5-1-TRAIL-DR5-2-DR5-3). More negative E-values indicate higher predicted affinity, and the E-value difference between successive states (delta-E) tracks the effect of oligomerisation. An identical run without the test compound served as a ligand-free control at each state. Cross-check: the dimer ranking was verified with AutoDock Vina 1.2 on the same receptor coordinates, using a 26 A cubic box centred on the interfacial cleft, exhaustiveness 8, nine binding modes and a 3 kcal/mol energy range. Ligands were built from canonical SMILES, protonated at pH 7.4 and minimised with MMFF94. One job was run per ligand with no fixed random seed, so Vina scores are not bit-reproducible. Interaction analysis: docked poses were inspected in BIOVIA Discovery Studio Visualizer v20.1.0.19295 to list contact residues and interaction types; contacts with DR5 and with TRAIL were catalogued to test interface bridging. EXPERIMENTAL WORKFLOW (binding assay) A fluorescence-based solid-phase ligand-receptor assay was adapted from an ELISA-type format. Recombinant human DR5 (Assay Genie, RPCB0398) was coated at 2 ug/mL (40 uL/well) in carbonate buffer pH 9.6 onto high-binding 96-well plates and blocked with 3% BSA. Recombinant human TRAIL (Assay Genie, RPCB1575) was labelled with FITC at a TRAIL:FITC molar ratio of 1:5 for 1 h at 37 C in the dark; free dye was removed by centrifugal ultrafiltration (Amicon Ultra, 10 kDa MWCO). Soluble DR5 (2 ug/mL, 30 uL) and TRAIL-FITC (4 ug/mL, 30 uL) were added, and reactions ran at 37 C in 100 uL with DMSO at or below 1% v/v. Each compound (ellagic acid, umbelliferone, gallic acid, coumarin; 10 mM DMSO stocks) was tested at 12.5, 25, 50 and 100 uM in duplicate wells on a single plate, with blank, negative, positive and DMSO controls. TRAIL-FITC retained after PBST washing was read on a GloMax Discover reader (Promega) at 475 nm excitation and 500 to 550 nm emission. Percent binding, referenced to the positive control (100%), was fitted to a three-parameter logistic model by nonlinear least squares (SciPy curve_fit, Python). Raw and processed files for every step are in the matching folders of this deposit; the README gives the layout and the reuse caveats.

Institutions

Categories

Chemistry, Biophysics, Computational Medicinal Chemistry, Apoptosis, Death Receptor, Molecular Docking, Computational Chemistry, Cancer Drug Development, TNF Related Apoptosis-Inducing Ligand Therapy

Funders

  • Directorate of Research, Technology, and Community Service (DRTPM), Ministry of Higher Education, Science, and Technology of the Republic of Indonesia
    Grant ID: No. 224/C3/DT.05.00/PL-BARU/2026

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