RFdiffusion (de-novo backbone generation)

Overview

RFdiffusion (Watson et al., Nature 2023; RosettaCommons/RFdiffusion) is a diffusion model that generates protein backbones — new 3D structures, not sequences. It supports unconditional generation, motif scaffolding (build a fold around a fixed functional motif), binder design (generate a backbone that binds a target surface), and symmetric assemblies. It is the structure-generation step that starts the de-novo design pipeline; alterlab-proteinmpnn then designs sequences for the backbone and alterlab-alphafold validates them.

When to Use This Skill

Use this skill when the user wants to:

• Generate a novel protein backbone from scratch (unconditional).
• Scaffold a functional motif (e.g. a binding loop / catalytic geometry) into a new fold.
• Design a binder backbone against a given target protein surface / hotspots.
• Build symmetric oligomers (cyclic/dihedral) as backbones.