# Modeling enzyme temperature stability from sequence segment perspective

arXiv: https://arxiv.org/abs/2507.19755 · HTML: https://mlsanity.com/paper/2507.19755/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 2 of its 51 references that are in the map.
- First posted on arXiv 26 Jul 2025.

## Builds on (most cited first, 2 of 2)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [ProtTrans: Towards Cracking the Language of Life's Code Through Self-Supervised Deep Learning and High Performance Computing](https://mlsanity.com/paper/2007.06225/) (2020)

## Abstract (arXiv)

Developing enzymes with desired thermal properties is crucial for a wide range of industrial and research applications, and determining temperature stability is an essential step in this process. Experimental determination of thermal parameters is labor-intensive, time-consuming, and costly. Moreover, existing computational approaches are often hindered by limited data availability and imbalanced distributions. To address these challenges, we introduce a curated temperature stability dataset designed for model development and benchmarking in enzyme thermal modeling. Leveraging this dataset, we present the textitSegment Transformer, a novel deep learning framework that enables efficient and accurate prediction of enzyme temperature stability. The model achieves state-of-the-art performance with an RMSE of 24.03, MAE of 18.09, and Pearson and Spearman correlations of 0.33, respectively. These results highlight the effectiveness of incorporating segment-level representations, grounded in the biological observation that different regions of a protein sequence contribute unequally to thermal behavior. As a proof of concept, we applied the Segment Transformer to guide the engineering of a cutinase enzyme. Experimental validation demonstrated a 1.64-fold improvement in relative activity following heat treatment, achieved through only 17 mutations and without compromising catalytic function.