AI3SD Video: The "almost druggable" genome
Tudor Ionel Oprea · ePrints Soton (University of Southampton) · 2021
This talk will briefly introduce the "Illuminating the Druggable Genome" knowledge management center, with focus on its protein-centric data aggregator, Pharos (https://pharos.nih.gov/), and the DrugCentral online pharmaceutical compendium (https://drugcentral.org/). Using Pharos/DrugCentral data, we then examine the question, "what proteins that could potentially be ligandable, are currently not?", in a disease context. To do this, we examine proteins available in the RSCB PDB (https://www.rcsb.org/) – the "PDB-ome" => 347 proteins that lack known ligands; Proteins for which chemical matter is known, N=2644 - the "SAR-ome" => of these, 115 proteins meet the "ligandable" criteria; the "Pocket-ome", i.e., proteins that have a close - by sequence identity - homologue with known 3D structure, which leads to ~700 ligandable proteins with PDB structures; 180 that have close homologues but lack 3D structures; and N=2623 proteins that could be modeled with reasonable confidence; last but not least, the "Phen-ome", which looks at this entire list (N = 6742) from the perspective of rare and common diseases, GWAS and mouse phenotype data, etc, and narrows down the previous lists. The "almost druggable genome" contains 715 ligandable (3D exists) proteins, 180 proteins for which chemical matter is likely to be found, and at least 100 proteins that could be subject to chemical probe optimization.