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From Words to Amino Acids: Does the Curse of Depth Persist?

arXiv:2602.21750v11 citationsh-index: 16
Originality Incremental advance
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This work identifies a potential inefficiency in widely used protein language models, which could impact their scalability and efficiency in applications like protein engineering and design.

The study investigated whether protein language models (PLMs) suffer from depth inefficiency similar to the 'Curse of Depth' observed in large language models, finding consistent patterns across six PLMs where later layers contribute less to predictions, especially in deeper models.

Protein language models (PLMs) have become widely adopted as general-purpose models, demonstrating strong performance in protein engineering and de novo design. Like large language models (LLMs), they are typically trained as deep transformers with next-token or masked-token prediction objectives on massive sequence corpora and are scaled by increasing model depth. Recent work on autoregressive LLMs has identified the Curse of Depth: later layers contribute little to the final output predictions. These findings naturally raise the question of whether a similar depth inefficiency also appears in PLMs, where many widely used models are not autoregressive, and some are multimodal, accepting both protein sequence and structure as input. In this work, we present a depth analysis of six popular PLMs across model families and scales, spanning three training objectives, namely autoregressive, masked, and diffusion, and quantify how layer contributions evolve with depth using a unified set of probing- and perturbation-based measurements. Across all models, we observe consistent depth-dependent patterns that extend prior findings on LLMs: later layers depend less on earlier computations and mainly refine the final output distribution, and these effects are increasingly pronounced in deeper models. Taken together, our results suggest that PLMs exhibit a form of depth inefficiency, motivating future work on more depth-efficient architectures and training methods.

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