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

Aleena Siji, Amir Mohammad Karimi Mamaghan, Ferdinand Kapl, Tobias Höppe, Emmanouil Angelis, Andrea Dittadi, Maurice Brenner, Michael Heinzinger, Karl Henrik Johansson, Kaitlin Maile, Johannes von Oswald, Stefan Bauer

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Track: long paper (4–8 pages excluding references)

Keywords: protein language models, depth analysis, representation learning

TL;DR: We systematically analyze depth usage in protein language models across 6 model families for 20 variants.

Abstract: 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.

Anonymization: This submission has been anonymized for double-blind review via the removal of identifying information such as names, affiliations, and identifying URLs.

Submission Number: 29