AI4Proteins: The “almost druggable” genome – Professor Tudor Oprea

This seminar forms part of the AI3SD and RSC-CICAG AI4Proteins Series. This series is sponsored by Arctoris and Schrödinger.

This video is the twelfth talk in the Protein Structure Prediction Conference.

The “almost druggable” genome – Professor Tudor Oprea

Abstract: 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.

Bio: Tudor Oprea is Professor and Chief, Translational Informatics Division, Department of Internal Medicine, UNM School of Medicine, Albuquerque, New Mexico (USA); and Guest Professor at the universities of Gothenburg (Sweden) and Copenhagen (Denmark). He holds an MD PhD from the University of Medicine and Pharmacy, Timişoara, Romania. Dr. Oprea co-authored over 260 publications, 10 US patents, and edited 2 books on drug discovery. His current research is to develop validated artificial intelligence models for target selection in drug discovery by combining numerical and text-mined information to model human health. Oprea serves as PI for the Illuminating the Druggable Genome Knowledge Management Center.

Further details from this series can be found at: https://www.ai3sd.org/ai4proteins

This video is an output from the AI3SD Network+ (Artificial Intelligence and Augmented Intelligence for Automated Investigations for Scientific Discovery) which is funded by EPSRC under Grant Number EP/S000356/1

DOI Link: http://dx.doi.org/10.5258/SOTON/P0105