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ProteinBench: A Holistic Evaluation of Protein Foundation Models

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arxiv 2409.06744 v2 pith:VG6EZGEL submitted 2024-09-10 q-bio.QM cs.AIcs.LGq-bio.BM

classification q-bio.QMcs.AIcs.LGq-bio.BM
keywords proteinevaluationmodelsfoundationframeworkholisticperformanceproteinbench
verification ladder T0 review T1 audit T2 compute T3 formal
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Recent years have witnessed a surge in the development of protein foundation models, significantly improving performance in protein prediction and generative tasks ranging from 3D structure prediction and protein design to conformational dynamics. However, the capabilities and limitations associated with these models remain poorly understood due to the absence of a unified evaluation framework. To fill this gap, we introduce ProteinBench, a holistic evaluation framework designed to enhance the transparency of protein foundation models. Our approach consists of three key components: (i) A taxonomic classification of tasks that broadly encompass the main challenges in the protein domain, based on the relationships between different protein modalities; (ii) A multi-metric evaluation approach that assesses performance across four key dimensions: quality, novelty, diversity, and robustness; and (iii) In-depth analyses from various user objectives, providing a holistic view of model performance. Our comprehensive evaluation of protein foundation models reveals several key findings that shed light on their current capabilities and limitations. To promote transparency and facilitate further research, we release the evaluation dataset, code, and a public leaderboard publicly for further analysis and a general modular toolkit. We intend for ProteinBench to be a living benchmark for establishing a standardized, in-depth evaluation framework for protein foundation models, driving their development and application while fostering collaboration within the field.

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Forward citations

Cited by 6 Pith papers

Reviewed papers in the Pith corpus that reference this work. Sorted by Pith novelty score. Full citation record

  1. Improving Protein Sequence Design through Designability Preference Optimization

    cs.LG 2025-05 conditional novelty 6.0 of 10

    A residue-level preference optimization method that uses AlphaFold pLDDT scores as rewards triples the in silico design success rate of LigandMPNN on enzyme benchmarks.

  2. Designing Cyclic Peptides via Harmonic SDE with Atom-Bond Modeling

    cs.LG 2025-05 conditional novelty 6.0 of 10

    CpSDE generates cyclic peptides of all four cyclization types for a protein pocket by alternating a harmonic-SDE structure denoiser with a residue-type predictor.

  3. Antigen-specific Antibody Multi-modal Foundation Model for Functional Antibody Design

    q-bio.BM 2026-07 reject novelty 5.0 of 10

    AAMFM combines ESM3, an antigen-geometry adapter, and Cal-DPO preference optimization rewarded by AlphaFold3-style scores to design antibody CDRs and structures, reporting higher predicted binding scores than prior methods.

  4. Protein-SE(3): Benchmarking SE(3)-based Generative Models for Protein Structure Design

    cs.LG 2025-07 conditional novelty 5.0 of 10

    Protein-SE(3) is a unified benchmark that retrains six SE(3) protein backbone generative models on the same data and evaluates them with identical metrics for designability, diversity, and novelty.

  5. PFMBench: Protein Foundation Model Benchmark

    q-bio.BM 2025-06 conditional novelty 5.0 of 10

    A comprehensive benchmark of 17 protein foundation models across 38 tasks yields task correlations, a streamlined protocol, and identifies ProTrek as the strongest general performer.

  6. AffinityFlow: Guided Flows for Antibody Affinity Maturation

    cs.LG 2025-02 reject novelty 5.0 of 10

    AffinityFlow guides AlphaFlow structure generation toward low Rosetta binding energy, then inverse-folds the structures to propose antibody mutations, and reports top scores on a computational affinity maturation benchmark.

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