Data from: Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule

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.

本仓库包含论文《寡聚化使小分子可选择性靶向内在无序区域》（Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule）的源数据、分析结果与元数据。本数据集覆盖核磁共振（Nuclear Magnetic Resonance, NMR）实验（含化学位移扰动Chemical Shift Perturbations, CSPs、顺磁弛豫增强Paramagnetic Relaxation Enhancements, PREs）、动态光散射、微量热泳动、浊度/饱和浓度c_sat、基于高效液相色谱（High Performance Liquid Chromatography, HPLC）的小分子分配实验、荧光/微分干涉差（Differential Interference Contrast, DIC）显微镜成像、荧光漂白恢复（Fluorescence Recovery After Photobleaching, FRAP），以及基于乳糖阻遏蛋白LacI的细胞拴定测定实验。本仓库提供原始仪器导出文件、处理后的表格（CSV/XLSX格式）、图像文件（TIFF/JPEG/LSM/CZI格式）与分析脚本（Python/R语言编写），各子文件夹均配有专属README文档，所有文件按图片及图组进行分类整理。蛋白质主链核磁共振归属数据已提交至生物磁共振数据库BMRB（Biological Magnetic Resonance Data Bank），相关登录号详见本仓库的README文档。本仓库未包含任何可识别个人身份的信息或敏感数据。内在无序区域（Intrinsically Disordered Regions, IDRs）因缺乏类药分子的稳定结合位点，成为极具挑战性的药物靶点。本研究针对首个进入临床试验的靶向IDR的小分子展开探究，发现该小分子可选择性结合该蛋白的寡聚化形式——该构象较单体状态更具结构化，且通过带有螺旋倾向性区域内的芳香族残基相互作用得以稳定。此外，该化合物可改变调控靶蛋白构象集合的相互作用网络，进而影响其作为转录因子所关联的凝聚特性。本研究结果为开发靶向内在无序区域的小分子药物策略提供了系统性的理论框架。