# PON-Tm: A Sequence-Based Method for Prediction of Missense Mutation Effects on Protein Thermal Stability Changes

## TL;DR

PON-Tm is a new method that predicts how protein mutations affect thermal stability using sequence data and environmental factors.

## Contribution

PON-Tm introduces a sequence-based approach that outperforms existing methods by integrating language model features and environmental variables.

## Key findings

- PON-Tm outperformed four established methods in predicting thermal stability changes.
- The method integrates features from a protein language model and environmental factors like pH.
- A web server was developed to provide easy access to PON-Tm.

## Abstract

Proteins, as crucial macromolecules performing diverse biological roles, are central to numerous biological processes. The ability to predict changes in protein thermal stability due to mutations is vital for both biomedical research and industrial applications. However, existing experimental methods are often costly and labor-intensive, while structure-based prediction methods demand significant computational resources. In this study, we introduce PON-Tm, a novel sequence-based method for predicting mutation-induced thermal stability variations in proteins. PON-Tm not only incorporates features predicted by a protein language model from protein sequences but also considers environmental factors such as pH and the thermostability of the wild-type protein. To evaluate the effectiveness of PON-Tm, we compared its performance to four well-established methods, and PON-Tm exhibited superior predictive capabilities. Furthermore, to facilitate easy access and utilization, we have developed a web server.