Protein FID: improved evaluation of protein structure generative models

MOTIVATION: Protein structure generative models have seen a recent surge of interest, but meaningfully evaluating them computationally is an active area of research. While current metrics have driven useful progress, they do not capture how well models sample the design space represented by the training data. We argue for a protein Frechet Inception Distance (FID) metric to supplement current evaluations with a measure of distributional similarity in a semantically meaningful latent space. RESULTS: Our FID behaves desirably under protein structure perturbations and correctly recapitulates similarities between protein samples: it correlates with optimal transport distances and recovers FoldSeek clusters and the CATH hierarchy. Evaluating current protein structure generative models with FID shows that they fall short of modeling the distribution of PDB proteins. AVAILABILITY: Code is available at: https://github.com/ffaltings/protfid.

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Publication Details

Journal
Bioinformatics
Published
2026-04-01
DOI
https://doi.org/10.1093/bioinformatics/btag156
Primary Topic
Protein Structure and Dynamics
Type
article
Field-Weighted Citation Impact
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article

Protein FID: improved evaluation of protein structure generative models

Regina Barzilay, Tommi Jaakkola, Felix Faltings, Hannes Stark
Bioinformatics
Protein Structure and Dynamics
article

Protein FID: improved evaluation of protein structure generative models

Regina Barzilay, Tommi Jaakkola, Felix Faltings, Hannes Stark
article en

Abstract

MOTIVATION: Protein structure generative models have seen a recent surge of interest, but meaningfully evaluating them computationally is an active area of research. While current metrics have driven useful progress, they do not capture how well models sample the design space represented by the training data. We argue for a protein Frechet Inception Distance (FID) metric to supplement current evaluations with a measure of distributional similarity in a semantically meaningful latent space. RESULTS: Our FID behaves desirably under protein structure perturbations and correctly recapitulates similarities between protein samples: it correlates with optimal transport distances and recovers FoldSeek clusters and the CATH hierarchy. Evaluating current protein structure generative models with FID shows that they fall short of modeling the distribution of PDB proteins. AVAILABILITY: Code is available at: https://github.com/ffaltings/protfid.

BioinformaticsVol. 42(4)
IIT@MIT (US)
Openalex Percentile: Top 28%
Protein Structure and Dynamics
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