Tutorial.md

DrugDomain database Tutorial

DrugDomain database includes two types of hierarchy: protein and molecule-centric. The complete lists of proteins and small molecules can be accessed through the top menu. The protein or molecule can be searched using the search field on the main page. The search can be conducted using UniProt or DrugBank accession numbers:

Search result for the UniProt accession P07949 (http://prodata.swmed.edu/DrugDomain/proteins/data/P07949.html) is shown below. Each protein page includes UniProt accession, gene name, protein name and table of molecules and drugs that target this protein protein. The list of molecules includes links to DrugDomain data webpages, DrugBank accession, molecule name, drug action data from DrugBank, affinity data from BindingDB, InChI Key, and SMILES formula:

Search result for the DrugBank accession DB00398 (http://prodata.swmed.edu/DrugDomain/molecules/data/DB00398.html) is shown below. Each molecule page lists the DrugBank accession, molecule name, InChI Key, SMILES formula, and small molecule PDB accession followed by the list of human proteins that are targets for this molecule. The list of proteins includes links to DrugDomain data webpages, UniProt accession, drug action data from DrugBank, protein names, and affinity data from BindingDB:

DrugDomain data webpage (for example: http://prodata.swmed.edu/DrugDomain/data/P07949_DB15822.html) contains DrugBank accession, molecule name, InChI Key, SMILES formula, small molecule PDB accession, and drug action data from DrugBank followed by the table of PDB structures and/or AF models with target particular protein. The table contains different information depending on the availability of experimentally determined 3D protein structures together with a particular DrugBank molecule. For cases with known PDB structure that includes DrugBank molecule and target protein DrugDomain data webpage's table includes PDB accession linked to RCSB, downloadable PyMOL script, an indication that this interaction between molecule and protein target was confirmed experimentally, a list of ECOD domains interacting with the molecule with links to the ECOD database, names of corresponded ECOD X-groups (possible homology level) and 2D diagrams of ligand–protein interactions (LigPlots):

The PyMOL script downloads the PDB structure from RCSB, colors ECOD domains by different colors, colors residues interacting with the molecule in magenta:

DrugDomain data webpage for cases without experimental PDB structure that includes DrugBank molecule and target protein includes AF accession, downloadable PyMOL script, an indication that this interaction between molecule and protein target was not confirmed experimentally (and was predicted), a list of ECOD domains interacting with the molecule with links to the AF-based ECOD database and names of corresponded ECOD X-groups:

The PyMOL script in these cases includes the AF model, colors it by ECOD domains, colors residues interacting with the molecule in magenta:

DrugDomain data webpage also includes link to list of drug binding-associated post-translational modifications (PTMs) where available (see above). For example: http://prodata.swmed.edu/DrugDomain/PTMs/data/P68104_DB04315_PTMs.html. This table includes information about each PTM and links to PyMOL sessions with models of modified proteins generated by AlphaFold3, RoseTTAFold All-Atom or Chai-1. PyMOL sessions include mapped ECOD domains shown in various colors and modified residue and ligand shown in magenta:

Files available for download

DrugDomain v1.0 (these files did not change in new version v1.1):
http://prodata.swmed.edu/DrugDomain/download/DrugDomain_v1.0_data_PDBs_ECODv291.txt - domain annotations for all human proteins that are targets for small molecules and drugs from DrugBank and that have experimentally determined PDB structures http://prodata.swmed.edu/DrugDomain/download/DrugDomain_v1.0_data_AlphaFill.txt - domain annotations for all human proteins that are targets for small molecules and drugs from DrugBank and that DO NOT have experimentally determined PDB structures

DrugDomain v1.1:
http://prodata.swmed.edu/DrugDomain/download/AllPTMs_per_residue_with_ligs.txt - list of all identified small molecule binding-associated PTMs
http://prodata.swmed.edu/DrugDomain/download/PTMs_pdb_structures_ECOD_domains_with_ligs.txt - domain annotations for identified small molecule binding-associated PTMs in PDB structures
http://prodata.swmed.edu/DrugDomain/download/PTMs_alphafill_models_ECOD_domains_with_ligs.txt - domain annotations for identified small molecule binding-associated PTMs in AlphaFill models
http://prodata.swmed.edu/DrugDomain/download/PTMs_test_set_models.tar.gz - PTM-modified protein models for the test set (see our preprint for details: https://www.biorxiv.org/content/10.1101/2025.01.14.633078)
http://prodata.swmed.edu/DrugDomain/download/PTMs_our_set_models.tar.gz - PTM-modified protein models for the DrugDomain database set