DOI: 10.5061/dryad.w9ghx3g3s
title: Data from: Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule

description: 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.
description: # Data from: Oligomerization enables the selective targeting of an
 intrinsically disordered region by a small molecule Dataset DOI:
 [10.5061/dryad.w9ghx3g3s](https://doi.org/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
 **c**sat; 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.