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MI-PEFT: Mixture-of-Experts Integrated Parameter-Efficient Fine-Tuning Protein Language Models Improves Acidophilic Proteins Classification

Honghan Shen
Sep 2026 · 0 citations · 37 references
Biology Computer Science

Abstract

Acidophilic proteins that remain stable and functional under highly acidic conditions, are important for industrial biocatalysis, acid-related bioprocessing, and the discovery of acid-stable enzymes. However, their identification relies heavily on time-consuming experimental screening methods. With the rapid growth of protein sequence databases, the need for computational identification methods that are both accurate and efficient has become stronger. The emergence of protein language models (PLMs) has significantly improved the sequence representation of downstream biological prediction tasks. This paper proposes MI-PEFT, a mixture-of-experts integrated parameter-efficient fine-tuning framework. Built on the ESM C-600M backbone, the framework incorporates LoRA-based PEFT methods and a DeepSeekMoE-based classification head to resolve the limitations of PEFT and significantly improve computational efficiency. Notably, this task is characterized by a significant class imbalance in the dataset, making high specificity particularly challenging. The experimental results demonstrate that MI-PEFT on PLMs, especially {\text{C}}^{\text{3}}\text{A}, serves as an efficient tool for identifying acidophilic proteins and a constrained pathway that helps resolve class-imbalance by preserving the pretrained representations.

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