Navigating Interactions for Drug Discovery: All ligands great & small - Seth Harris (Genentech, USA)

Navigating Interactions for Drug Discovery: All ligands great and small (and the in-between macrocycles) To facilitate the usage and access to emerging computational methods that are transforming numerous areas of structural biology, we have built a multi-module platform (termed Sol, encompassing GYST, GYDE, and MARS) that aids in structure analyses, protein engineering and de novo design, and proteome-scale annotations for target assessment in research and drug discovery. This talk will highlight key features of the platform with a focus toward ligand interaction and binding pocket annotations, and the utility of their varied representations and navigation thereof in drug discovery. Additionally, an emphasis on macrocyclic binders will describe particular benefits and a few challenges in their data handling and tooling, as illustrated through vignettes from recently published work on the USP7 deubiquitinase and an interesting inhibitor in the complement cascade of the immune system. This brief treatise on macrocycle discovery will highlight the current incarnation of our platform, the path towards its collaborative release, and the evolving landscape of agentic interaction with structural data.