DUDE

This is the Wiki Page for DUD-E, a directory of useful decoys - enhanced. DUD-E is on the web at http://dude.docking.org.

This page contains documentation, FAQ, and may be used for posting errors and ommissions in DUD-E, and also for commenting on the database's design and usefulness.

Detailed file documentation

General comments

First, you may not need any of these files. They are provided in an attempt to be completely transparent, but the "all" files linked on the DUDE website contains the files you should need: receptor, crystal ligand, actives (isomeric SMILES, mol2 and SDF) and decoys (same three formats)

File by file, folder by folder explanations

• Folders like P29274, P30543, or P46616 : these are swissprot codes. The directories contains preparation files specific to that individual code, which is often species specific.

• Docking, docking_auto

• dudgen_clustered, dudgen_ecfp4 - The clustered sets live in dudgen_clustered while the full raw sets are in dudgen_ecfp4. Inside, the ligands.charge file contains the mapping from chembl ids to unique property sets, and the search/decoys.*.picked contain the actual decoys for that protonation set.

The file formats are as follows:

• ligands.charge - gives unique protonation states of input ligands.

Format: one ligand protonation form per line
SMILES input_id protonation_id mwt logp rb hba hbd charge

• search/
  • decoys.<protonation_id>.picked - contains matched decoys for each unique ligand protonation state

Format: ligand protomer and then 50 matched decoys
first line: ligand SMILES input_id protonation_id
SMILES ZINC_ID ZINC_Protonation_ID

• actives_* including: actives_combined.ism, actives_final.ism, actives_murcko_1.ism, actives_murcko_1_30_nM.ism, actives_murcko_enumeration.ism, actives_nM_chembl.ism, actives_nM_combined.ism, actives_scaffolds.ism, actives_trimmed.txt, actives_final.mol2.gz, actives_final.sdf.gz

• common_scaffolds.ism

• crystal_ligand.mol2

• decoys_*, including: decoys_final.ism, decoys_scaffolds.ism, decoys_tabbed.ism, decoys_to_scaffolds.ism, decoys_final.mol2.gz, decoys_final.sdf.gz

• inactives_*, including: inactives_combined.ism, inactives_nM_chembl.ism, inactives_nM_combined.ism

• marginal_* including: marginal_actives_combined.ism, marginal_actives_nM_chembl.ism, marginal_actives_nM_combined.ism, marginal_inactives_combined.ism, marginal_inactives_nM_chembl.ism, marginal_inactives_nM_combined.ism

• pdb_analyze.txt pdb_blessed.txt

• receptor.pdb

• scaffold_count.txt

• subset_decoys.py in the target directory can covert the full dudgen_ecfp4 set into a dudgen_clustered type set given a list of molregno ids.

• uniprot.txt

FAQ

Q1. How duplicates are removed

In the paper, you said "We then remove duplicate decoys from the ligand set by sorting decoys from least to most duplicated and assigned each decoy to the protonated ligand which has the least number of decoys already assigned." I don't know which molecules you considered as duplicates, and how to define and calculate the similarity. Please explain!

A1. Duplicate removal procedure

Decoys are uniquely identified by their ZINC protonation ids. We ensure that a particular protonation id (prot_id) is only assigned to one ligand of a given target.

• 0) After filtering the for the 25% most dissimilar decoys
• 1) map each prot_id to the number of different ligands it could be assigned to
• 2) sort from the prot_ids that hit the fewest ligands to those that hit the most
• 3) loop over that sorted list, starting with the most constrained decoys
• 4) assign each prot_id to the the ligand with the fewest other prot_ids so far

The effect is to spread the decoys as evenly as possible among the ligands they could belong to.

Q2. Weird residue labeling in receptor.pdb files

I have noticed some weird residue labeling in the PDB files on the DUDE website, what is that all about? e.g.

• comt: Residues #168/9 are labeled as DIC/ASZ respectively. In the original PDB file they are labeled as ASP/ASN.

• cp2c9: Residues 58/61 are labeled as NMA/ACE. The original PDB has different labeling (I couldn't figure out the mapping).

• jak2: Residues 160/1/2 are labeled as PTR which is labeled as HETATM in the original PDB file. Also, there are missing residues between PRO156 and PTR160 that appear in the original PDB file (GLN, ASP, LYS, GLU).

• pde5a: Residues 653/4 are labeled as HIZ/DID where the original PDB file contains HIS/ASP.

A2. PDB receptor file residue labeling

These are the actual preparations we used in DOCK itself. As explained in the paper, many of the targets have been enhanced to help docking performance. The non-standard residues most typically change the partial charges, which is used for metal-coordination and dipole "tarting". See docking/grids/prot.table.ambcrg.ambH in that targets directory for how the residue is being interpreted.

These are not errors, and represent over 6 months of work to improve DUD-E for DOCK. Some of these improvements are likely transferable to other docking programs (waters retained, ASN flips, etc.). The original PDB code is provided if trying to translate this information to another docking protocol is too much of a hassle.

The funky names help to make our manual intervention explicit and transparent.

Q3. More on duplicate IDs

In a number of decoy sets there are duplicate ids. So, for example, the decoys in try1 contain

Cc1ccc(cc1Cl)NC(=O)C(=O)NN/C(=C\C(=O)Nc2ccc(cc2)NC(=O)C)/C C02343192
Cc1ccc(cc1Cl)NC(=O)C(=O)NN/C(=C/C(=O)Nc2ccc(cc2)NC(=O)C)/C C02343192

Where the same id refers to the different stereochemistry. My question is why was this design decision taken (to have both in the decoys file)? Perhaps a single entry with undefined stereochemistry at the differing position might be an alternative, or if two entries have different stereochemistry because they can be synthesised that way a suffix in the id would have been helpful "C02343192_1", "C02343192_2". Taking the representation in ZINC (in this case the bottom one) is also another possibility - but then where does the top one come from?

Q3. Answers on duplicate IDs

The uniqueness of decoys is enforced at the level of protonation ids. At the time it was generated, there were 2 protomer ids for that zinc substance id.

decoys.F91123300.picked:
Cc1ccc(cc1Cl)NC(=O)C(=O)NN/C(=C\C(=O)Nc2ccc(cc2)NC(=O)C)/C C02343192       P94844827
Cc1ccc(cc1Cl)NC(=O)C(=O)NN/C(=C/C(=O)Nc2ccc(cc2)NC(=O)C)/C C02343192       P98798844

Only the second protomer remains now. So this was an error in ZINC that was later fixed. I expect these kinds of source errors to show up in both ChEBML and ZINC.

Community Feedback

This space is reserved for community users to comment or discuss DUD-E. Please feel free to use this resource to communicate with other DUD-E users. You may also write to the authors, and we may then adapt our correspondence into an entry on this page.

END OF FAQ