Accelerating protein degrader discovery: Computational strategies for degrader design and optimization

Protein degraders have emerged as a promising modality in drug discovery, offering a novel mechanism for modulating protein function by leveraging the cell’s natural degradation pathways. However, designing protein degraders presents unique challenges due to their bifunctional nature, requiring complex optimization across multiple parameters.

Schrödinger has engaged in collaborative research projects with industry scientists to develop computational workflows that can accurately predict the structure of ternary complexes between two protein partners and a bifunctional molecule. In this webinar, we will showcase Schrödinger’s advanced computational toolkit, which integrates protein-protein docking and linker sampling to generate an ensemble of possible complexes, metadynamics to accurately score these complexes, and free energy perturbation (FEP+) calculations to optimize degrader potency.

Join us to explore how these workflows can accelerate the design of protein degraders—from predicting ternary complexes to optimizing linker properties—and can empower real-time collaboration through Schrödinger’s LiveDesign platform.

Webinar Highlights:

• Summary of current trends and challenges in the modeling of protein degraders
• Overview of Schrödinger computational solutions, including exit vector sampling, ternary complex ensemble prediction and filtering using experimental information like HDX-MS, ternary complex scoring, and linker optimization using FEP+
• Demo of workflows in LiveDesign to streamline the degrader design process
• Sneak peak of upcoming Maestro panels for protein degrader modeling