CatIF-RL: Activity-Oriented Enzyme Sequence Design by Steered Inverse Protein Folding (opens in new tab)

Protein inverse folding models are designed to generate amino acid sequences compatible with a given backbone structure, but they are not explicitly optimized for specific biological functions. Here, we present CatIF-RL, a framework that steers a graph-based denoising diffusion inverse folding model toward designing enzyme variants with enhanced catalytic activity. CatIF-RL first adapts the inverse folding model to enzyme structural data, then introduces activity-oriented preference signals u...