Computer-Driven Discovery of GPCR Ligands with New Chemotypes and Functional Selectivity

Explore a presentation from MolSoft's UGM 2023 by Dr. Vsevolod "Seva" Katritch of USC, focusing on computer-driven discovery of GPCR ligands with new chemotypes and functional selectivity. Delve into structure-function relationships and ligand design for GPCRs, core computational technologies, and the design of bitopic ligands for μ-Opioid Receptor. Learn about modulating functional pathways of μ-Opioid receptor by targeting conserved Na* site and discover ongoing and emerging directions in rational structure-based ligand design. Examine major breakthroughs in structure-based virtual ligand screening, including the use of REAL Space for on-demand virtual libraries. Understand proposed acceleration approaches, such as utilizing chemical modularity of REAL libraries and the importance of binding pose in selecting minimal fragments. Gain insights into V-SYNTHES computational benchmarking, analogs-by-catalog optimization, and collaborative applications to diverse targets. Explore Enamine Libraries' evolution from HTS to V-SYNTHES, custom combinatorial libraries based on SuFEx "click" reaction, and the development of novel Angiotensin AT2 antagonists for neuropathic pain, from discovery to (pre)clinical candidate stage.