Title: Soft Non-Diagonality Penalty Enables Latent Space-Level Interpretability of pLM at No Performance Cost
Primary area: unsupervised, self-supervised, semi-supervised, and supervised representation learning
Keywords: Peptides, representation learning, contrastive learning

Abstract: Emergence of large scale protein language models (pLMs) has led to significant performance gains in predictive protein modeling. However, it comes at a high price of interpretability, and efforts to push representation learning towards explainable feature spaces remain scarce. The prevailing use of domain-agnostic and sparse encodings in such models fosters a perception that developing both parameter-efficient and generalizable models in a low-data regime is not feasible. In this work, we explore an alternative approach to develop compact models with interpretable embeddings while maintaining competitive performance. With the BiLSTM-AE model as an example trained on positional property matrices, we introduce a soft weight matrix non-diagonality penalty. Through Jacobian analysis, we show that this penalty aligns embeddings with the initial feature space while leading to a marginal decrease in performance on a suite of four common peptide biological activity classification benchmarks. Moreover, it was demonstrated that the use of one-hot encoded sequence clustering-based contrastive loss to produce semantically meaningful latent space allows to further improve benchmarking performance. The use of amino acid physicochemical properties and DFT-derived cofactor interaction energies as input features provides a foundation for intrinsic interpretability, which we demonstrate on fundamental peptide properties. The resulting model is over 33,000 times more compact than the state-of-the-art pLM ProtT5. It demonstrates performance stability across diverse benchmarks without task-specific fine-tuning, showcasing that domain-tailored architectural design can yield highly parameter-efficient models with fast inference and preserved generalization capabilities.