# Protein Language Model Zero-Shot Fitness Predictions are Improved by Inference-only Dropout

arXiv: https://arxiv.org/abs/2506.14793 · HTML: https://mlsanity.com/paper/2506.14793/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 3 of its 7 references that are in the map.
- First posted on arXiv 31 May 2025.

## Builds on (most cited first, 3 of 3)

- [Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning](https://mlsanity.com/paper/1506.02142/) (2015)
- [A Baseline for Detecting Misclassified and Out-of-Distribution Examples in Neural Networks](https://mlsanity.com/paper/1610.02136/) (2016)
- [Uncertainty as a Predictor: Leveraging Self-Supervised Learning for Zero-Shot MOS Prediction](https://mlsanity.com/paper/2312.15616/) (2023)

## Abstract (arXiv)

Protein Language Models (PLMs) such as ESM2 have been shown to be capable of zero-shot prediction of critical scalar properties of proteins (fitness). In this work, we show that injecting a dropout layer at inference time between a PLM's featurizer/embedding layer and its transformer, and averaging its output akin to Monte-Carlo dropout increases zero-shot performance on a subset of the ProteinGym dataset. This is the case even when the model was not trained with dropouts to begin with, and does not require retraining or finetuning of the PLM. A dropout of 0.1 seems performant across all models.