PTM-Mamba: a PTM-aware protein language model with bidirectional gated Mamba blocks.

Current protein language models (LMs) accurately encode protein properties but have yet to represent post-translational modifications (PTMs), which are crucial for proteomic diversity and influence protein structure, function and interactions. To address this gap, we develop PTM-Mamba, a PTM-aware protein LM that integrates PTM tokens using bidirectional Mamba blocks fused with ESM-2 protein LM embeddings via a newly developed gating mechanism. PTM-Mamba uniquely models both wild-type and PTM sequences, enabling downstream tasks such as disease association and druggability prediction, PTM effect prediction on protein-protein interactions and zero-shot PTM discovery. In total, our work establishes PTM-Mamba as a foundational tool for PTM-aware protein modeling and design.