ProteinMPNN (fixed-backbone sequence design)

Overview

ProteinMPNN (Dauparas et al., Science 2022; dauparas/ProteinMPNN) solves the inverse-folding problem: given a protein backbone (a 3D structure with no or a placeholder sequence), it designs amino-acid sequences predicted to fold to that backbone. It is fast, robust, runs on CPU, and is the standard "sequence" step between backbone generation (alterlab-rfdiffusion) and structure validation (alterlab-alphafold).

When to Use This Skill

Use this skill when the user wants to:

• Inverse-fold a backbone PDB into one or more candidate sequences.
• Redesign only selected positions while fixing the rest (partial design).
• Enforce symmetry by tying residues/chains so homo-oligomers get identical sequences.
• Bias the amino-acid composition (e.g. avoid cysteines) or use the soluble model.
• Produce the sequence step of a design → fold → score loop.