gEDES-HM (generalized Ensemble Docking with Enhanced sampling of pocket Shape - Homology Modeling)

Homology modeling and HADDOCK3 docking of adenylate kinases.

gEDES-HM transfers a conformational ensemble generated by enhanced-sampling simulation of one protein to its homologues by multi-template homology modeling. This repository holds the scripts, modeling inputs, docking results and analysis data for its validation on 22 adenylate kinase homologues.

Paper: Kurt et al., J. Chem. Inf. Model. 2026, 66, 13586-13596.

The ensemble itself comes from the gEDES protocol: vargiulab/gEDES, Basciu et al., J. Chem. Inf. Model. 2025.

GitHub and Zenodo

The complete archive is on Zenodo: 10.5281/zenodo.21534586. This repository has the same layout, without the structure ensembles, which are too large for git (710 MB).

	GitHub	Zenodo
scripts/, analysis/, docking/	yes	yes
proteins_structural_models/: MODELLER drivers, alignments, RMSD wrappers	yes	yes
proteins_structural_models/: templates, models, references (*.pdb.gz)	no	yes

To run the steps that need the structures, download proteins_structural_models.zip from Zenodo and unpack it at the top of this repository:

curl -L -o proteins_structural_models.zip https://zenodo.org/records/21534586/files/proteins_structural_models.zip
unzip -n proteins_structural_models.zip

These work from this repository alone:

cd analysis/tableS6_check && bash check_tableS6.sh
cd analysis/statistics && python3 gEDES_SI_statistics.py

Contents

README.md
proteins_structural_models/   modeling inputs, one folder per system, 1 to 22
  gEDES/  apo/  holo/
docking/                      HADDOCK3 results, all four receptor conditions
analysis/                     computed data behind the reported numbers
scripts/                      workflow scripts

Each subdirectory has its own README with the detail: docking/README.md for the file naming and the columns of the ranking tables, analysis/README.md for the data tables and how to regenerate them, scripts/README.md for the workflow.

The four receptor conditions

Label	Where	Receptors per target
HM_gEDES	gEDES/, docking/<n>_*	101 homology models from the gEDES representatives, DOPE-selected
HM_4AKE(apo)	apo/, docking/APO_*	10 models from the single apo template, PDB 4AKE
HM_1AKE(holo)	holo/, docking/HOLO-1ake_*	10 models from the single holo template, PDB 1AKE
HOLO_expt	docking/redocking_HOLO-expt_*	1, the target's own experimental holo receptor, ligand removed

The first two were in the original submission. HM_1AKE(holo) and HOLO_expt were added in revision as controls: the first bounds what the transferred ensemble can achieve given an experimental bound structure of the reference protein, which a prospective application would not have; the second is the redocking ceiling and the noise floor of the RMSD metrics.

22 systems, 26 complexes

Files are keyed by system number, 1 to 22. Four targets carry two ligands each and were docked as separate complexes, so a ligand suffix distinguishes them: system 2 _ADP / _AMP, system 9 _ADP / _AMP, system 15 _ADP182 / _ADP183, system 21 _ADP214 / _ADP215. That is why the 22 systems give 26 complexes throughout.

System	Target	System	Target
1	A0A0J9X1X4	12	Q9UIJ7
2	Q6LTE1	13	Q04ML5
3	P84139	14	P27144
4	P16304	15	P9WKF5
5	P07170	16	A0A2R2JFU6
6	P27142	17	Q68EH2
7	Q6B341	18	M4AA20
8	O66490	19	A0A2R2JFU5
9	Q8IJV6	20	A0A452CSM2
10	P43188	21	5G3Y (PDB)
11	P08760	22	5G3Z (PDB)

UniProt accessions unless marked as PDB. Systems 21 and 22 are synthetic constructs without UniProt entries.

Notes

• Structures are PDB format, many gzipped; .tsv files are tab separated.
• The binding-site definition for a given target is the BS_RESIDUES value in its run_calc_rmsd-cpptraj*.sh, and is the same at the modeling and the docking stage.
• Nothing under analysis/ contains an absolute path. Set ADK_ARCHIVE_ROOT only if you separate it from the rest of the archive.

Citation

If you use gEDES-HM, please cite the paper:

Kurt H, Athar M, Basciu A, Reys V, Bonvin AMJJ, Vargiu AV. Mapping Functional Transitions across Protein Homologues from a Single Simulation: Application of gEDES-HM to Adenylate Kinases. J. Chem. Inf. Model. 2026, 66 (20), 13586-13596. https://doi.org/10.1021/acs.jcim.6c02521

The full data archive:

Kurt H, Athar M, Vargiu A. Mapping functional transitions across protein homologues from a single simulation: application of gEDES-HM to adenylate kinases. Zenodo, 2026. https://doi.org/10.5281/zenodo.21534586

License

CC-BY-4.0, the same as the Zenodo archive. See LICENSE.