DOI: 10.6084/m9.figshare.27826488
title: Data for <b>HEAD_TED</b>

description: # HEAD_TED Data Collections<br>## Data Inventory<br>This collection comprises a set of files generated and utilized in our study. The following archives and tables are included:<br>- [x] Raw_conformations.tar.gz<br>- [x] Mininplace_conformations.tar.gz<br>- [x] All_results_extended_tables.tar.gz<br>- [x] PoseBusters_detailed_results.tar.gz<br>- [x] LigBoundConf_TED_PoseCheck.csv<br>- [x] GM-5K_mmff94_min.sdf.tar.gz<br>- [x] GM-5K_collection.csv<br>- [x] GM-1K_mmff94_min.sdf.tar.gz<br>- [x] GM-1K_collection.csv<br>- [x] DFT-5K.sdf.tar.gz<br>- [x] DFT-5K.csv<br>- [x] Suppl_stat_num_mols.csv<br><br>## Data File Descriptions<br>### Pre- and Post-Optimization Conformations<br>The `Raw_conformations.tar.gz` archive contains the initial, unoptimized molecular conformations generated by 5 models in `.sdf` format. Correspondingly, the `Mininplace_conformations.tar.gz` archive houses the same set of molecules following in situ refinement using OPLS3e force field with protein pocket fixed. Within each `.sdf` file, individual molecular entries are distinguished by unique identifiers embedded in the molecule headers. Each archive contains five independent `.sdf` files, with filenames corresponding to the different generative models employed.<br><br>### Extended Results Tables<br>The `All_results_extended_tables.tar.gz` archive encompasses six independent `.csv` files, five of them named according to the generative model used and the last one named with DUDE which ONLY includes the properties of positive molecules in DUDE dataset employed in SI Figure.3. These five tables provide a comprehensive overview of the generated molecules, with the following columns:<br><br>- **mol_id**: Unique identifier extracted from the header of each molecule block in the respective `.sdf` file.<br>- **smiles**: Simplified Molecular Input Line Entry System (SMILES) representation of the molecule.<br>- **model**: The generative model responsible for producing the molecule.<br>- **pdb_id**: The Protein Data Bank (PDB) identifier of the protein target pocket from which the binding site information was derived.<br>- **qed**: Quantitative Estimate of Drug-likeness (QED) score, calculated using RDKit.<br>- **sas**: Synthetic Accessibility (SA) score, calculated using RDKit.<br>- **mol_weight**:  Molecular Weight, calculated using RDKit.<br>- **logp**: Wildman-Crippen LogP, calculated using RDKit.<br>- **tpsa**: Topological Polar Surface Area, calculated using RDKit.<br>- **Fsp3**: Fraction of C atoms that are SP3 hybridized, calculated using RDKit.<br>- **#Amide**: Number of Amide bonds, calculated using RDKit.<br>- **#ChiralCenter**: Number of chiral centers, calculated using RDKit.<br>- **#RotatableBonds**: Number of rotatable bonds excluding amide or ester bonds, calculated using RDKit.<br>- **mininplace_failure**: A binary indicator of the success of the local optimization process within the binding pocket:<br>    - `0`: Optimization was successful.<br>    - `1`: Optimization failed.<br>- **raw_PoseBusters_ligand_protein_interaction_invalidity**: A binary indicator assessing the validity of ligand-protein interactions in the unoptimized conformation, as determined by PoseBusters:<br>    - `0`: Valid interaction geometry.<br>    - `1`: Invalid interaction geometry.<br>- **raw_PoseBusters_ligand_conformation_invalidity**: A binary indicator assessing the validity of the ligand's internal conformation in the unoptimized state, as determined by PoseBusters:<br>    - `0`: Valid ligand conformation.<br>    - `1`: Invalid ligand conformation.<br>- **min_PoseBusters_ligand_protein_interaction_invalidity**: A binary indicator assessing the validity of ligand-protein interactions in the minimized conformation, as determined by PoseBusters:<br>    - `0`: Valid interaction geometry.<br>    - `1`: Invalid interaction geometry.<br>- **min_PoseBusters_ligand_conformation_invalidity**: A binary indicator assessing the validity of the ligand's internal conformation in the minimized state, as determined by PoseBusters:<br>    - `0`: Valid ligand conformation.<br>    - `1`: Invalid ligand conformation.<br>- **HEAD_ligand_protein_interaction_invalidity**: An indicator assessing the validity of ligand-protein interactions in the unoptimized conformation, as determined by HEAD:<br>    - `0`: Valid interaction geometry.<br>    - `1`: Invalid interaction geometry.<br>    - `-1`: Unsupported conformation that may contain elements out of {H, C, N, O, F, S, Cl} or encounter unexpected error during loading<br>- **HEAD_ligand_conformation_invalidity**: An indicator assessing the validity of the ligand's internal conformation in the unoptimized state, as determined by HEAD:<br>    - `0`: Valid ligand conformation.<br>    - `1`: Invalid ligand conformation.<br>    - `-1`: Unsupported conformation that may contain elements out of {H, C, N, O, F, S, Cl} or encounter unexpected error during loading<br>- **TED_torsion_energy_irrationality**: An indicator of the plausibility of the predicted torsion energy, as determined by TED:<br>    - `0`: Torsion energy is considered rational.<br>    - `1`: Torsion energy is considered irrational.<br>    - `-1`: The conformation is unsupported by the TED model.<br>The original, detailed output files from the PoseBusters analysis are provided in the compressed archive `PoseBusters_detailed_results.tar.gz`. This archive contains 10 independent `.csv` files, detailing the results for all analyzed conformations, encompassing both the raw and the in situ optimized structures.<br><br><br>### LigBoundConf Extension Data<br>The `LigBoundConf_TED_PoseCheck.csv` file contains data used for the comparative analysis of PoseCheck and TED on a set of optimized ligand-bound conformations. The columns are defined as follows:<br><br>- **mol_id**: The ligand identifier as used in the original LigBoundConf publication.<br>- **LCSE**: The Local Conformational Strain Energy value (in kcal/mol) as reported in the original LigBoundConf publication.<br>- **TED_torsion_energy_irrationality**: As described in the "Extended Results Tables" section.<br>- **PoseCheck_strain_energy**: The strain energy calculated by PoseCheck (units should be specified if known, e.g., kcal/mol).<br><br>### GM-5K and GM-1K Subsets<br>The GM-5K and GM-1K datasets represent subsets of 5,000 and 1,000 molecules, respectively, extracted from the larger collection. In addition to the original conformations, this release includes two new compressed `.sdf` archives containing conformations optimized using the MMFF94 force field: `GM-5K_mmff94_min.sdf.tar.gz` and `GM-1K_mmff94_min.sdf.tar.gz`. The molecule headers within these optimized `.sdf` files retain the identifiers corresponding to the raw conformations in the original datasets, facilitating direct comparison.<br><br>Detailed DFT single-point energies (for both the original and MMFF94-optimized conformations), along with HEAD analysis results, are provided in the `.csv` files `GM-1K_collection.csv` and `GM-5K_collection.csv`.<br><br>Besides the columns mentioned above, the other columns in the `GM-1K_collection.csv` file are explained as follows:<br><br>- **DFT_single_point_energy_raw**: Single-point energy (in kcal/mol) of the unoptimized raw conformation calculated using Density Functional Theory (DFT).<br>- **DFT_single_point_energy_min**: Single-point energy (in kcal/mol) of the MMFF94-optimized conformation calculated using Density Functional Theory (DFT).<br>- **dE**: The energy difference (ΔE=E_raw−E_opt) in kcal/mol, representing the change in energy upon MMFF94 optimization.<br>- **HEAD_invalid_atoms**: A list detailing any atoms flagged as invalid by HEAD, along with the associated high-energy response value (in kcal/mol). If no invalid atoms are detected, this field contains None. For example: [(2, 'C', 40.962)] indicates that carbon atom number 2 (indexed from 1) was flagged with a high-energy response of 40.962 kcal/mol (Note: this energy value is a relative indicator and may not represent the absolute energy).<br>- **information_entropy_label**: A binary indicator where 1 signifies an invalid conformation detected solely by the information entropy approach; otherwise, 0.<br><br>The `GM-5K_collection.csv` file includes all the columns mentioned above for `GM-1K_collection.csv`, as well as the following additional columns:<br><br>- **MM/GBSA**: Binding free energy (in kcal/mol) estimated using the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) method, where the Amber ff14SB force field was used for protien and the General Amber Force Field  2 (GAFF2) for organic molecules. Lower (more negative) values indicate stronger predicted binding.<br>- **HEAD_E_bind**: Binding energy (in kcal/mol) calculated using the HEAD. This metric evaluates the stability of the ligand-receptor complex, with more negative values reflecting stronger interactions.<br>- **PoseCheck_num_clashes**: Number of steric clashes detected in the docked pose by PoseCheck. Clashes occur when atoms are positioned too closely, leading to unfavorable van der Waals repulsions. Lower values indicate better structural compatibility between the ligand and receptor.<br>- **SMINA_docking_score**: Docking score computed by SMINA. More negative scores suggest higher predicted binding affinity.<br>- **DrugPose_score**: Score assessing the drug-likeness and conformational suitability of the docked pose, generated by DrugPose. <br>- **DrugPose_ligand_protein_interaction_invalidity**: A binary indicator where 1 signifies an invalid conformation detected solely by the information entropy approach; otherwise, 0.<br><br>### DFT-5K<br>The conformations of DFT-5K dataset are provided in the `DFT-5K.sdf.tar.gz` archive. All molecules in this file have been optimized using the DFT method with appropriate constraints on specific dihedrals. Their single-point energies are re-calculated using a higher-level DFT method than used for optimization.<br><br>Each torsion fragment in DFT-5K is represented by 24 conformations, grouped under the same name in the header, corresponding to different dihedral angle values ranging from -180° to 180° in 15° increments (-180° is equivalent to 180°). Each molecule block in the `.sdf` file includes the following properties:<br>- **TORSION_ATOMS**: Indicese of atom quartet defining the specific dihedral, starting from 0.<br>- **DIHEDRAL_ANGLE**: The degree of the dihedral being investigated.<br>- **DFT_SINGLE_POINT_ENERGY**: Single-point energy (in kcal/mol) calculated using DFT method.<br><br>In addition to the `.sdf` file, the dataset includes a `DFT-5K.csv` file containing the following columns:<br>- **DFT_id**: The name in the header of each molecule block in `.sdf` file. Conformations with different dihedral angles of the same torsion fragment share the same DFT_id.<br>- **xTB_dih_relative_energies**: A string of relative energies, joined by `--`, representing the energies of the conformations optimized with constraints and calculated using GFN2-xTB. The order of energies corresponds to dihedral angles from -180° to 180° in 15°  increments (24 values in total). **Note**: These are relative energies, calculated by subtracting the minimum energy value among the 24 conformations, different from the single-point energies listed in previous sections.<br>- **model_dih_relative_energies**: Similar to the above, but the relative energies are predicted by TED-Model.<br><br>### Suppl_stat_num_mols.csv<br>This CSV file provides detailed statistics of molecules generated by five AI models (Lingo3DMolv, Pocket2Mol, PocketFlow, TargetDiff, PMDM) for 102 targets from the DUD-E dataset. For each target, the file lists the total number of molecules generated, the number of drug-like molecules, and the number of successfully minimized drug-like molecules. This dataset supports the evaluation of AI molecular generation efficiency and coverage across targets.<br>