aiqbench analysis
PFArena establishes a critical benchmark for evaluating how protein language models and LLMs perform in realistic wet-lab decision-making scenarios. The study reveals that while PLMs excel at single-mutant generation using biological priors, LLM-based agents outperform in multi-mutant ranking when specific fitness data is available, though all approaches struggle with expanding search spaces. This work provides essential metrics for researchers aiming to integrate AI into high-throughput protein engineering pipelines.
PFArena: Benchmarking Language Models for Protein Modification
arXiv:2609.28921v1 Announce Type: new Abstract: Protein modification requires navigating an immense sequence space, yet wet-lab validation remains low-throughput and costly. Although computational paradigms including protein language models (PLMs), large language models (LLMs), and LLM-based agents have shown promise in protein modification, their relative efficacy across realistic experimental decision-making settings remains unclear. To bridge this gap, we introduce PFArena, a benchmark comprising four controlled task interfaces that cover single-mutant generation and multi-mutant ranking. By providing varying levels of mutation fitness data, PFArena reflects four representative research scenarios characterized by differing degrees of prior experimental context. We assess six PLMs, six LLMs, and five LLM-based agents using complementary metrics to measure both peak and overall protein modification performance. Our evaluation reveals that model performance shifts systematically with the availability of target-specific experimental evidence: PLMs demonstrate proficiency in open-ended single-mutant generation by leveraging protein-specific priors, whereas LLMs and agents perform strongly in multi-mutant ranking, particularly when target-specific fitness data are available. Nevertheless, all model families face fundamental challenges with increasing search-space size and mutation depth. We release our code and benchmark suite to facilitate reproducible research in model-assisted protein modification.
Abstract:Protein modification requires navigating an immense sequence space, yet wet-lab validation remains low-throughput and costly. Although computational paradigms including protein language models (PLMs), large language models (LLMs), and LLM-based agents have shown promise in protein modification, their relative efficacy across realistic experimental decision-making settings remains unclear. To bridge this gap, we introduce PFArena, a benchmark comprising four controlled task interfaces that cover single-mutant generation and multi-mutant ranking. By providing varying levels of mutation fitness data, PFArena reflects four representative research scenarios characterized by differing degrees of prior experimental context. We assess six PLMs, six LLMs, and five LLM-based agents using complementary metrics to measure both peak and overall protein modification performance. Our evaluation reveals that model performance shifts systematically with the availability of target-specific experimental evidence: PLMs demonstrate proficiency in open-ended single-mutant generation by leveraging protein-specific priors, whereas LLMs and agents perform strongly in multi-mutant ranking, particularly when target-specific fitness data are available. Nevertheless, all model families face fundamental challenges with increasing search-space size and mutation depth. We release our code and benchmark suite to facilitate reproducible research in model-assisted protein modification.
Artificial Intelligence (cs.AI); Biomolecules (q-bio.BM)
arXiv:2609.28921 [cs.AI]
(or arXiv:2609.28921v1 [cs.AI] for this version)
https://doi.org/10.48550/arXiv.2609.28921 Focus to learn more arXiv-issued DOI via DataCite (pending registration)
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