Data from: Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule
Data files
Dec 17, 2025 version files 2.27 GB
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Fig_1_EPI001_Selectivity_NRADs.zip
156.71 KB
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Fig_2_EPI001_interacts_with_oligomers.zip
187.92 KB
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Fig_3_ARAD_Interaction_Network.zip
8.50 MB
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Fig_4_Tau5__forms_interaction_site.zip
189.27 KB
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Fig_5_EPI001_partitioning.zip
146.36 MB
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Fig_6_EPI001_Rigidifies_Condensates.zip
1.22 GB
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README.md
4.71 KB
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SI_1_NRADs_SeqProps_NMR.zip
784.51 KB
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SI_2_DLS_Oligomerization_Delta2D_NMR.zip
287 KB
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SI_3_NMRdata_CSP_Matrices_PRE.zip
4.47 MB
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SI_4_Tau5__Mutants_oligomerization_EPI001.zip
266.13 KB
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SI_5_Imaging_Tc_Partitioning_Tether.zip
663.42 MB
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SI_6_EPI001_Rigidification_condensates_csat.zip
228.54 MB
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SI_7_Tau-5__Mutant_Controls_MST.zip
264.12 KB
Abstract
This repository contains the source data, analysis outputs, and metadata for “Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule.” Datasets span NMR (CSPs, PREs), dynamic light scattering, microscale thermophoresis, turbidity/c_sat, HPLC-based small-molecule partitioning, fluorescence/DIC microscopy, FRAP, and a cell-based LacI tethering assay. Raw instrument exports, processed tables (CSV/XLSX), images (TIFF/JPEG/LSM/CZI), and analysis scripts (Python/R) are provided with per-folder READMEs. Files are organized by figure/panel. Protein backbone NMR assignments are deposited in BMRB; accession numbers are listed in the repository README. No personally identifiable or sensitive data are included.
Intrinsically disordered regions (IDRs) are challenging drug targets because they lack stable interaction sites for drug-like molecules. We studied the first small molecule targeting an IDR to be evaluated in a clinical trial and found that it interacts selectively with an oligomeric form of the protein, more structured than the monomeric state, that is stabilized by interactions involving aromatic residues in regions with helical propensity. We also found that this compound alters the network of interactions defining the conformational ensemble of its target, thus affecting its condensation properties, linked to its function as a transcription factor. These findings provide a framework for developing strategies to target intrinsically disordered regions with small molecules.
Dataset DOI: 10.5061/dryad.w9ghx3g3s
Description of the data and file structure
Title: Data for “Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule”
Overview
Source data underlying Figures 1–6 and Supplementary Figures S1–S7, including NMR chemical shifts/CSPs and helix populations, DLS size distributions and monomer fractions, HPLC chromatograms, EPI-001 partitioning/ c_sat, FRAP quantifications and time-lapse imaging, PRE datasets, MST traces, and intact-MS adduct timecourses.
File & folder structure
Files are organized by manuscript figures. Each ZIP contains raw exports and processed tables used to generate the corresponding panels.
- Fig_1_EPI001_Selectivity_NRADs.zip — NR AD sequence properties; per-residue CSPs of NR ADs ± EPI-001; EPI-001 1H peak shifts ± proteins.
- Fig_2_EPI001_interacts_with_oligomers.zip — AR AD oligomerization vs EPI-001 CSP correlation; DLS monomer % for AR AD/Tau-5* across EPI-001 titrations; fragment CSPs; EPI-001 1H shifts with fragments; 1Tau-5* vs 2Tau-5* DLS/helix population/CSPs induced by EPI-001.
- Fig_3_ARAD_Interaction_Network.zip — Reciprocal-fragment CSP matrices (apo and +EPI-001) and ΔCSP matrices; allTau-5 intermolecular PRE (Γ₂ and ΔΓ₂) with raw intensity/R₂ fits.
- Fig_4_Tau5__forms_interaction_site.zip — Tau-5* mutant CSPs ± EPI-001 and mutant oligomerization CSPs (25→400 µM); intact-MS adduct kinetics (AR fragments, allTau-5 single-Cys, Tau-5* mutants); Cys pK_a by 13Cβ NMR.
- Fig_5_EPI001_partitioning.zip — HPLC-derived EPI-001 partition coefficients (P) for NR ADs, AR fragments, Tau-5* mutants; LacI-tether imaging (raw CZI; processed data; analysis code) and RNAPII-CTD/YFP enrichment quantifications.
- Fig_6_EPI001_Rigidifies_Condensates.zip — Confocal fluorescence images for AR AD/allTau-5/Tau-5* ± EPI-001; allTau-5 fusion time-lapse; FRAP datasets & videos (raw ROI traces and t½); helix population for Tau-5* vs Tau-5*:EPI-001 adduct; allTau-5 csat; fluorescence images of Tau-5* mutants.
- SI_1_NRADs_SeqProps_NMR.zip — Extended sequence analysis, AR AD CSPs induced by MR AD and in AR AD+EPI-001 with MR AD, and helix populations for NR ADs.
- SI_2_DLS_Oligomerization_Delta2D_NMR.zip — NR AD DLS (monomer %, Z-avg d, intensity traces); EPI-001 titrations; 1Tau-5*/2Tau-5* DLS; AR AD fragments helix population.
- SI_3_NMRdata_CSP_Matrices_PRE.zip — Reciprocal 1H–15N NMR CSP tables for AR AD fragment pairs (apo/+EPI-001); derived CSP² and ΔCSP² matrices; AR AD C404 intra/inter PRE and allTau-5 inter-PRE datasets with I_para/I_dia, Γ₂, ΔΓ₂ and underlying intensities/R₂ fits.
- SI_4_Tau5__Mutants_oligomerization_EPI001.zip — Tau-5* mutant helix population; DLS Tau-5* titration, CSPs ± EPI-001; oligomerization CSPs (25→400 µM).
- SI_5_Imaging_Tc_Partitioning_Tether.zip — In-vitro fluorescence/DIC imaging (raw & processed); Tc turbidity curves; HPLC chromatograms for P; LacI-tether processed images and per-cell intensities.
- SI_6_EPI001_Rigidification_condensates_csat.zip — condensate fusion movies (Tau-5* and AR-AD) ± EPI-001; Tau-5* CSPs for reversible vs covalent EPI-001; allTau-5 Tc ± EPI-001; aspect-ratio analysis of Tau-5* mutant condensates.
- SI_7_Tau-5__Mutant_Controls_MST.zip — Tau-5* mutant helix-breaker controls (L436P vs T435P) for oligomerization; MST traces for 2Tau-5* vs EPI-001.
Notes
- Units: All NMR chemical shifts (δ) are in ppm; DLS sizes in nm; monomer % from intensity-weighted size distributions.
- CSPs: Computed from 1H/15N amide shifts with standard 15N scaling (Δ15N/5).
External accessions
Protein backbone NMR assignments (BMRB):
MR AD (53098, 53099), PR AD (53112), GR AD (53097), ERα AD (53096), Nt L26P (53108), Tau-5* (53105), Tau-5* C404 (53104), 1Tau-5* (53114), 2Tau-5* (53113), noAro (53100), A398P (53101), C404Y (53106), AAA (53102), G407A (53103), Tau-5*:EPI-001 adduct (53115), allTau-5 24G (53109), allTau-5 CtoS (53110), allTau-5 CtoS PP (53111); amide ^1H/^15N chemical shifts for Tau-5* mutants: h2SA (53116), h3A (53117), L436P (53118), A398P+L436P (53119).
Contacts
- Corresponding: xavier.salvatella@irbbarcelona.org
- First author: bielskute.s@gmail.com
Curation note
Per-ZIP, figure-specific READMEs (conditions, file/column definitions, and analysis steps) are being added. More information can be find in the Methods of the manuscript.