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

Publication ,  Journal Article
Peng, FZ; Wang, C; Chen, T; Schussheim, B; Vincoff, S; Chatterjee, P
Published in: Nature methods
May 2025

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.

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Published In

Nature methods

DOI

EISSN

1548-7105

ISSN

1548-7091

Publication Date

May 2025

Volume

22

Issue

5

Start / End Page

945 / 949

Related Subject Headings

  • Software
  • Proteomics
  • Proteins
  • Protein Processing, Post-Translational
  • Humans
  • Developmental Biology
  • Computational Biology
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 10 Technology
 

Citation

APA
Chicago
ICMJE
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Peng, F. Z., Wang, C., Chen, T., Schussheim, B., Vincoff, S., & Chatterjee, P. (2025). PTM-Mamba: a PTM-aware protein language model with bidirectional gated Mamba blocks. Nature Methods, 22(5), 945–949. https://doi.org/10.1038/s41592-025-02656-9
Peng, Fred Zhangzhi, Chentong Wang, Tong Chen, Benjamin Schussheim, Sophia Vincoff, and Pranam Chatterjee. “PTM-Mamba: a PTM-aware protein language model with bidirectional gated Mamba blocks.Nature Methods 22, no. 5 (May 2025): 945–49. https://doi.org/10.1038/s41592-025-02656-9.
Peng FZ, Wang C, Chen T, Schussheim B, Vincoff S, Chatterjee P. PTM-Mamba: a PTM-aware protein language model with bidirectional gated Mamba blocks. Nature methods. 2025 May;22(5):945–9.
Peng, Fred Zhangzhi, et al. “PTM-Mamba: a PTM-aware protein language model with bidirectional gated Mamba blocks.Nature Methods, vol. 22, no. 5, May 2025, pp. 945–49. Epmc, doi:10.1038/s41592-025-02656-9.
Peng FZ, Wang C, Chen T, Schussheim B, Vincoff S, Chatterjee P. PTM-Mamba: a PTM-aware protein language model with bidirectional gated Mamba blocks. Nature methods. 2025 May;22(5):945–949.

Published In

Nature methods

DOI

EISSN

1548-7105

ISSN

1548-7091

Publication Date

May 2025

Volume

22

Issue

5

Start / End Page

945 / 949

Related Subject Headings

  • Software
  • Proteomics
  • Proteins
  • Protein Processing, Post-Translational
  • Humans
  • Developmental Biology
  • Computational Biology
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 10 Technology