LC-SEPLM: long-range contact-supervised adaptation for sequence-only protein representation learning
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Abstract (arXiv)
Protein language models learn transferable sequence representations. However, because they primarily model contextual dependencies along amino-acid sequences, their training objectives do not explicitly constrain the model to learn three-dimensional residue contacts formed after folding . Here, we introduce LC-SEPLM (Long-range Contact-supervised ESM Protein Language Model), which adapts ESM2 with LoRA and long-range residue-pair contact supervision while retaining sequence-only downstream inference. Pair-specific queries use cross-attention over the complete sequence to extract global sequence context associated with long-range spatial contacts. To expose the model to diverse structural information, we trained LC-SEPLM on 500,000 AlphaFold Swiss-Prot proteins. In downstream evaluation, LC-SEPLM improved all eight protein-level tasks relative to ESM2. The largest gain occurred in remote-homology recognition, where macro-F1 increased from 0.6122 to 0.6769 (+0.0647, or 6.47 percentage points). On the official ESM-S EC benchmark, LC-SEPLM also outperformed ESM-S with a maximum absolute gain of 0.1771. These results support residue-pair contact supervision as a bounded route for introducing structural information into protein sequence representations while preserving sequence-only inference.
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References · 10
- 2017Attention Is All You Needcited by 60,361
- 2018BERT: Pre-training of Deep Bidirectional Transformers for Language Understandingcited by 40,399
- 2021LoRA: Low-Rank Adaptation of Large Language Modelscited by 14,380
- 2020Learning from Protein Structure with Geometric Vector Perceptronscited by 313
- 2019Evaluating Protein Transfer Learning with TAPEcited by 231
- 2022Structure-Aware Transformer for Graph Representation Learningcited by 194
- 2022Protein Representation Learning by Geometric Structure Pretrainingcited by 162
- 2016Accurate De Novo Prediction of Protein Contact Map by Ultra-Deep Learning Modelcited by 31
- 2024Endowing Protein Language Models with Structural Knowledgecited by 11
- 2024Structure-Informed Protein Language Modelcited by 6
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