Dataset ------- **TOUGH-M1** comprises experimental target structures with binding pockets identified by [Fpocket 2.0][1]. The following files are included: ### Lists **`TOUGH-M1_target.list`** A list of 7524 targets **`TOUGH-M1_pocket.list`** A list of pockets identified by [Fpocket 2.0][1] * 1st column is the PDB-ID of target protein * 2nd column is the index of the best pocket * 3rd column is the accuracy of the best pocket (Matthews correlation coefficient over binding residues) **`TOUGH-M1_positive.list`** A list of 505116 positive pairs. These proteins bind chemically similar ligands despite having dissimilar global sequences and structures. * The first two columns are the PDB-IDs of target proteins * 3rd column is the sequence identity between the targets * 4th column is the structure similarity ([TM-score][2] by [Fr-TM-align][3]) * 5th column is the chemical similarity of bound ligands (Tanimoto coefficient by [kcombu][4]) **`TOUGH-M1_negative.list`** A list of 556810 negative pairs. These proteins have dissimilar global sequences and structures and bind chemically dissimilar ligands. * The first two columns are the PDB-IDs of target proteins * 3rd column is the sequence identity between the targets * 4th column is the structure similarity ([TM-score][2] by [Fr-TM-align][3]) * 5th column is the chemical similarity of bound ligands (Tanimoto coefficient by [kcombu][4]) ### Data **`TOUGH-M1_dataset.tar.gz`** A tarball containing the following files ([11asA][5] as an example): * target structure in PDB format (`11asA.pdb`) * target structure in PDBQT format (`11asA.pdbqt`) * bound ligand in PDB format (`11asA00.pdb`) * bound ligand in PDBQT format (`11asA00.pdbqt`) * bound ligand in SDF format (`11asA00.sdf`) * protein-ligand contacts by [LPC][6] (`11asA00.lpc`) * pockets by [Fpocket][1] (`11asA.fpocket`) Results ------- Output files generated for the TOUGH-M1 dataset by several binding site alignment algorithms are available to facilitate comparative benchmarks. In addition, the conformations of 1515 drugs from the DrugBank database docked to TOUGH-M1 targets can be downloaded as well. Note that because of the large size of virtual screening data, docking conformations are split into 3 tarballs. Pocket matching and virtual screening calculations were conducted against pockets predicted by [Fpocket 2.0][1]. The following programs are included: ### Pocket alignment tools [APoc][7] **`APoc-TOUGH-M1_positive.score`** **`APoc-TOUGH-M1_negative.score`** PS-score and *p*-values for positive and negative pairs. **`APoc-TOUGH-M1_positive.tar.gz`** **`APoc-TOUGH-M1_negative.tar.gz`** Output files from [APoc v1.0b15][7] for positive and negative pairs. [G-LoSA][8] **`G-LoSA-TOUGH-M1_positive.score`** **`G-LoSA-TOUGH-M1_negative.score`** GA-score values for positive and negative pairs. **`G-LoSA-TOUGH-M1_positive.tar.gz`** **`G-LoSA-TOUGH-M1_negative.tar.gz`** Output files from [G-LoSA v2.1][8] for positive and negative pairs. [SiteEngine][9] **`SiteEngine-TOUGH-M1_positive.score`** **`SiteEngine-TOUGH-M1_negative.score`** Match score, Total score and T-score values for positive and negative pairs. **`SiteEngine-TOUGH-M1_positive.tar.gz`** **`SiteEngine-TOUGH-M1_negative.tar.gz`** Output files from [SiteEngine 1.0][9] for positive and negative pairs. ### Virtual screening [AutoDock Vina][10] **`Vina-TOUGH-M1_part1.tar.gz`** **`Vina-TOUGH-M1_part2.tar.gz`** **`Vina-TOUGH-M1_part3.tar.gz`** Docked conformations in PDBQT format. [rDock][11] **`rDock-TOUGH-M1_part1.tar.gz`** **`rDock-TOUGH-M1_part2.tar.gz`** **`rDock-TOUGH-M1_part3.tar.gz`** Docked conformations in SDF format. [1]: https://www.ncbi.nlm.nih.gov/pubmed/19486540 [2]: https://www.ncbi.nlm.nih.gov/pubmed/15476259 [3]: https://www.ncbi.nlm.nih.gov/pubmed/19077267 [4]: https://www.ncbi.nlm.nih.gov/pubmed/21736325 [5]: http://www.rcsb.org/pdb/explore.do?structureId=11AS [6]: https://www.ncbi.nlm.nih.gov/pubmed/10320401 [7]: https://www.ncbi.nlm.nih.gov/pubmed/23335017 [8]: https://www.ncbi.nlm.nih.gov/pubmed/26813336 [9]: https://www.ncbi.nlm.nih.gov/pubmed/15147845 [10]: https://www.ncbi.nlm.nih.gov/pubmed/19499576 [11]: https://www.ncbi.nlm.nih.gov/pubmed/24722481