Isaac Sappington

Improved protein binder design using -pairing targeted RFdiffusion

Conditioning RFdiffusion on edge beta-strand pairing yields specific binders to polar targets, with in silico success above 9.2% versus 0.98% for hotspot-only conditioning.

Computational design of pH-sensitive binders

This paper introduces computational methods to design pH-sensitive binders that dissociate under acidic conditions, demonstrating their application in targeting various receptors and proteins.

De novo design of miniprotein agonists and antagonists targeting G protein-coupled receptors

This paper presents computational methods for designing GPCR-binding miniproteins and validates them through high-throughput screening, producing agonists and antagonists for multiple GPCRs.

Designed Endocytosis-Triggering Proteins mediate Targeted Degradation and amplify signaling

The paper designs EndoTags to trigger endocytosis and degradation of target proteins, enabling tissue-specific targeting and therapeutic applications.

Broadly applicable and accurate protein design by integrating structure prediction networks and diffusion generative models

Fine-tuning RoseTTAFold as a diffusion denoiser gives RFdiffusion, a general protein backbone generator; a designed influenza haemagglutinin binder matched its model by cryo-EM.