
This Zenodo repository reflects a time-of-acceptance deposition of code and data associated with the manuscript Sequence and chemical specificity define the functional landscape of intrinsically disordered regions. Full citation information: Sequence and chemical specificity define the functional landscape of intrinsically disordered regions Iris Langstein-Skora1*, Andrea Schmid1*, Frauke Huth2*, Drin Shabani1, Lorenz Spechtenhauser1, Mariia Likhodeeva3, Franziska Kunert3, Felix J. Metzner3, Ryan J. Emenecker4,5, Mary O. Richardson5,6, Wasim Aftab7, Maximilian J. Götz1,8, Sarah K. Payer1,9, Niccoló Pietrantoni1,10, Valentina Sjeničić1,11, Sakthi K. Ravichandran1, Till Bartke12, Karl-Peter Hopfner3, Ulrich Gerland2, Philipp Korber1†, Alex S. Holehouse4,5† 1 Biomedical Center (BMC), Division of Molecular Biology, Faculty of Medicine, LMU Munich, Martinsried, Germany2 Physics of Complex Biosystems, Technical University of Munich, Garching, Germany3 Gene Center, Department of Biochemistry, LMU Munich, Munich, Germany4 Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA5 Center for Biomolecular Condensates, Washington University, St. Louis, MO, USA6 Present address: Moderna, Inc., Cambridge, MA, USA7 Core Facility Bioinformatics, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Martinsried, Germany8 Present address: Gene Center, Department of Biochemistry, LMU Munich, Munich, Germany9 Present address: Proteros Biostructures GmbH, Martinsried, Germany10 Present address: Scuola Superiore Sant’Anna, Pisa, Italy11 Present address: Faculty of Biology, University of Belgrade, Belgrade, Serbia12 Institute of Functional Epigenetics, Helmholtz Zentrum München, Neuherberg, Germany *These authors contributed equally†Corresponding author. Email: pkorber@lmu.de, alex.holehouse@wustl.edu The associated manuscript is pending formal acceptance, but the full citation information will be updated on the associated GitHub link that mirrors the code and content and most of the data in this Zenodo repository. Link: https://github.com/holehouse-lab/supportingdata/tree/master/2026/Langstein-Skora_2026 About Please seed the README.md file associated with the uploaded ZIP file. Contributors All authors listed above should be considered contributors to this work. Licensing DATA is shared under CC BY 4.0 (Creative Commons Attribution 4.0 International) (link here) CODE is shared under the MIT License. (link here) Funding Please see the ACKNOWLEDGEMENT section on the final publication for funder acknowledgement. File map The text below maps how each data element in the main/extended data maps to code and data within the repository. This information is also included in the main README.md associated with the .zip file. Figure 1 A - Schematic of conservation vs. disorder in a single protein (no data) B - figure_1/disorder_vs_conservation_correlation.ipynb C - figure_1/disorder_vs_conservation_correlation.ipynb D - figure_1/disorder_vs_conservation_correlation.ipynb E - Schematic of plasmid shuffling assay (no data) F - Data from dilution plates (see supplementary figures and supplementary tables) G - Schematic showing constructs (data from dilution plates) H - figure_1/abf1_idr2.fasta - amino acid sequence provided Figure 2 A - Schematic of chemical conservation vs. sequence conservation B - figures_2/composition_conservation.ipynb C - figures_2/alignment_schematic_figure_2c.ipynb D - growth data from dilution plates (see supplementary figures and supplementary tables). Tree structure from Feng et al. Scientific Reports 2017. E - growth data from dilution plates (see supplementary figures and supplementary tables) with protein function taken from UniProt and/or SGD entries on the proteins listed. Figure 3 A - Schematic showing folded domain and IDR; growth data from dilution plates (see supplementary figures and supplementary tables). B - Schematic showing what sequence "shuffling" means; growth data from dilution plates (see supplementary figures and supplementary tables). C - Schematic showing where subregions are being shuffled (schematic to scale); growth data from dilution plates (see supplementary figures and supplementary tables). D - figure_3/linear_analysis.ipynb E - Schematic highlighting relative positions of the essential motif, Abf1-G4-like subregion, and $Gal4G4 subregion. F - Files in figure_3/em_structural_prediction/ G - growth data from dilution plates (see supplementary figures and supplementary tables). H - Schematic (no data) I - growth data from dilution plates (see supplementary figures and supplementary tables). J - growth data from dilution plates (see supplementary figures and supplementary tables). K - growth data from dilution plates (see supplementary figures and supplementary tables). L - growth data from dilution plates (see supplementary figures and supplementary tables). M - growth data from dilution plates (see supplementary figures and supplementary tables). Figure 4 A - Schematic of motif and context (top) and chemical vs. sequence specificity (bottom) B - figure_4/coarse_grained_simulation_analysis.ipynb C - growth data from dilution plates (see supplementary figures and supplementary tables). D - figure_4/coarse_grained_simulation_analysis.ipynb E - growth data from dilution plates (see supplementary figures and supplementary tables). F - growth data from dilution plates (see supplementary figures and supplementary tables). G - growth data from dilution plates (see supplementary figures and supplementary tables). H - growth data from dilution plates (see supplementary figures and supplementary tables). I - figure_4/composition_analysis_fig_4.ipynb J - growth data from dilution plates (see supplementary figures and supplementary tables). K - growth data from dilution plates (see supplementary figures and supplementary tables). Figure 5 See readme in figure_5/ A - Schematic of FINCHES-based analysis B - Schematic of in silico evolution, with individual intermaps generated using figure_5/evolution/in_silico_evo.ipynb C - figure_5/evolution/signal_vs_noise_final.ipynb D - Schematic showing error-prone PCR workflow E - Schematic of expected behavior F (top) - figure_5/evolution/error_prone_pcr_analysis.ipynb F (bottom) - figure_5/evolution/error_prone_pcr_vs_in_silico_final.ipynb Figure 6 See readme in figure_6/ A - Schematic of MNase-seq B - figure_6/6B/MNase_coverage_Abf1_fig6B.xlsx C - Schematic of Anchor Away (no data) D - Schematic of ODM-seq (no data) E - figure_6/6E/6E_Kubik_responder_sites.tsv F - figure_6/6F/ G - figure_6/6F/ H - `Schematic of overall model (no data) Extended data Extended Data 1 A - figure_1/disorder_vs_conservation_correlation.ipynb B - extended_data_1/fig_s1_analysis.ipynb B inset - extended_data_1/fig_s1_analysis.ipynb C - extended_data_1/fig_s1_analysis.ipynb D - extended_data_1/fig_s1_analysis.ipynb E - extended_data_1/fig_s1_analysis.ipynb F - extended_data_1/fig_s1_analysis.ipynb G - Extended Data 2 A - extended_data_2/chip_figure.ipynb B - figure_2/composition_conservation.ipynb C - figure_2/composition_conservation.ipynb D - figure_2/composition_conservation.ipynb E - figure_2/composition_conservation.ipynb F - figure_2/composition_conservation.ipynb G - figure_2/composition_conservation.ipynb Extended Data 3 A - extended_data_3/ortholog_composition.ipynb B - figures_2 /compositional_analysis.ipynb C - extended_data_3/sequence_analysis_dead_seqs.ipynb D - extended_data_3/patterning_analysis.ipynb E - extended_data_3/patterning_analysis.ipynb F - extended_data_3/patterning_analysis.ipynb G - extended_data_3/sequence_alignment.docx (alignment using Needle). Extended Data 4 A - Schematic from simulation snapshot B - Parameter matrix C - figure_4/coarse_grained_simulation_analysis.ipynb D - figure_4/coarse_grained_simulation_analysis.ipynb E - Amino acid sequences F - extended_data_4/rad16_rad7_intermaps.ipynb G - extended_data_4/rad16_rad7_intermaps.ipynb H - extended_data_4/other_examples/signal_vs_noise_other_examples.ipynb Extended Data 5 See readme in extended_data_5/ A - extended_data_5/MNase_coverage_Abf1_ED5_A_B_C.xlsx B - extended_data_5/MNase_coverage_Abf1_ED5_A_B_C.xlsx C - extended_data_5/MNase_coverage_Abf1_ED5_A_B_C.xlsx D - extended_data_5/ED5_D/ED5_D_Kubik_responder_sites.tsv E - extended_data_5/ED5_E/ED5_E_Kubik_responder_sites.tsv F - extended_data_5/ED5_F/ED5_F_RNA_seq_boxplot_stat_v2.html Extended Data 6 See readme in extended_data_6/ A - extended_data_6/ED6_A/ED6_A_fixed_plus_one_grid_by_rep.tsv B - extended_data_6/ED6_B/ED6_B_spikein.tsv C - extended_data_6/ED6_C/ED6_C_k_resp_grid_by_rep.tsv Extended Data 7 See readme in extended_data_7/ A - extended_data_7/ED7_A_B_C/ED7_A_venn_diagram_invivo.tsv B - extended_data_7/ED7_A_B_C/ED7_B_venn_diagram_pwm.tsv C - extended_data_7/ED7_A_B_C/ED7_C_venn_diagram_pwm_vs_invivo.tsv D - extended_data_7/ED7_D_E_F_G/ED7_D_Hahn_bound_only.tsv E - extended_data_7/ED7_D_E_F_G/ED7_E_Hahn_resp_only.tsv F - extended_data_7/ED7_D_E_F_G/ED7_F_G_Hahn_bound_and_resp.tsv G - extended_data_7/ED7_D_E_F_G/ED7_F_G_Hahn_bound_and_resp.tsv Extended Data 8 See readme in extended_data_8/ A - extended_data_8/ED8_A/ B - extended_data_8/ED8_B/ C - extended_data_8/ED8_C/ D - extended_data_8/ED8_D/ E - extended_data_8/ED8_E/ Extended Data 9 A - extended_data_9/fus_sequences.fasta B - Schematic of a phase diagram C - Schematic of solving free energy surface for Flory-Huggins to build temperature-dependent phase diagrams D - extended_data_9/flory_huggins_phase_diagrams.ipynb E - extended_data_9/flory_huggins_phase_diagrams.ipynb F - extended_data_9/flory_huggins_phase_diagrams.ipynb G - extended_data_9/flory_huggins_phase_diagrams.ipynb H - extended_data_9/AF-Q13148-F1-model_v4.pdb - PDB structure for TDP-43 used to highlight helical residues 321-342 I - growth data from dilution plates (see supplementary figures and supplementary tables). Extended Data 10 A - extended_data_1/fig_s1_analysis.ipynb B - extended_data_1/fig_s1_analysis.ipynb C - extended_data_10/ED10_C/ED10_C_genome.tsv Supplementary information Supplementary figures 1 and 2 Growth data are provided in the viablity_data/ directory, with two large PDFs that report original images for growth plates. Supplementary tables For completeness, we also provide all supplementary tables in the supplementary_tables/ directory (supplementary_tables_2025_11_30.xlsx).
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