The Confessions of a Protein Language Model: Steering, Activations, and What Predicted Confidence Cannot Certify

Protein generate-and-screen pipelines use interventions and readouts to select candidates, but rarely test whether these track their intended targets. We audit published repetition steering, ESMFold confidence, and an activation readout. Steering preserves confidence at its operating point, but a fitted cliff follows at alpha_50 = 1.240x (sweep's own control: 64.0%). Direction matters at moderate matched-norm push, but not at saturation. Unsteered generator activations predict the confidence gate (ROC-AUC 0.786 +/- 0.004), supporting cost-aware, model-specific triage. We also replicate established length sensitivity, through which shortening can manufacture false nulls. Yet on composition- and length-matched design--scramble pairs, no balanced-accuracy interval excludes chance for experimental stability. Predicting the gate does not establish foldability. We should test what a readout measures before using it to select. Code and data: https://github.com/paninishah/plm-steering-audit

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-11-11
DOI
https://doi.org/10.64898/2026.11.10.765136
Primary Topic
Protein Structure and Dynamics
Type
preprint
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preprint

The Confessions of a Protein Language Model: Steering, Activations, and What Predicted Confidence Cannot Certify

Ruhina B. Karani, Meera Narvekar, Pearl Mody, Raj Panchali et al.
bioRxiv (Cold Spring Harbor Laboratory)
Protein Structure and Dynamics
preprint

The Confessions of a Protein Language Model: Steering, Activations, and What Predicted Confidence Cannot Certify

Ruhina B. Karani, Meera Narvekar, Pearl Mody, Raj Panchali, Mahek Sanghvi, Panini Shah
preprint en

Abstract

Protein generate-and-screen pipelines use interventions and readouts to select candidates, but rarely test whether these track their intended targets. We audit published repetition steering, ESMFold confidence, and an activation readout. Steering preserves confidence at its operating point, but a fitted cliff follows at alpha_50 = 1.240x (sweep's own control: 64.0%). Direction matters at moderate matched-norm push, but not at saturation. Unsteered generator activations predict the confidence gate (ROC-AUC 0.786 +/- 0.004), supporting cost-aware, model-specific triage. We also replicate established length sensitivity, through which shortening can manufacture false nulls. Yet on composition- and length-matched design--scramble pairs, no balanced-accuracy interval excludes chance for experimental stability. Predicting the gate does not establish foldability. We should test what a readout measures before using it to select. Code and data: https://github.com/paninishah/plm-steering-audit

bioRxiv (Cold Spring Harbor Laboratory)
Dwarkadas J. Sanghvi College of Engineering (IN)
Protein Structure and Dynamics
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