TY - JOUR
T1 - Unified Deep Learning of Molecular and Protein Language Representations with T5ProtChem
AU - Kelly, Thomas
AU - Xia, Song
AU - Lu, Jieyu
AU - Zhang, Yingkai
N1 - Publisher Copyright:
© 2025 The Authors. Published by American Chemical Society.
PY - 2025/4/28
Y1 - 2025/4/28
N2 - Deep learning has revolutionized difficult tasks in chemistry and biology, yet existing language models often treat these domains separately, relying on concatenated architectures and independently pretrained weights. These approaches fail to fully exploit the shared atomic foundations of molecular and protein sequences. Here, we introduce T5ProtChem, a unified model based on the T5 architecture, designed to simultaneously process molecular and protein sequences. Using a new pretraining objective, ProtiSMILES, T5ProtChem bridges the molecular and protein domains, enabling efficient, generalizable protein-chemical modeling. The model achieves a state-of-the-art performance in tasks such as binding affinity prediction and reaction prediction, while having a strong performance in protein function prediction. Additionally, it supports novel applications, including covalent binder classification and sequence-level adduct prediction. These results demonstrate the versatility of unified language models for drug discovery, protein engineering, and other interdisciplinary efforts in computational biology and chemistry.
AB - Deep learning has revolutionized difficult tasks in chemistry and biology, yet existing language models often treat these domains separately, relying on concatenated architectures and independently pretrained weights. These approaches fail to fully exploit the shared atomic foundations of molecular and protein sequences. Here, we introduce T5ProtChem, a unified model based on the T5 architecture, designed to simultaneously process molecular and protein sequences. Using a new pretraining objective, ProtiSMILES, T5ProtChem bridges the molecular and protein domains, enabling efficient, generalizable protein-chemical modeling. The model achieves a state-of-the-art performance in tasks such as binding affinity prediction and reaction prediction, while having a strong performance in protein function prediction. Additionally, it supports novel applications, including covalent binder classification and sequence-level adduct prediction. These results demonstrate the versatility of unified language models for drug discovery, protein engineering, and other interdisciplinary efforts in computational biology and chemistry.
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U2 - 10.1021/acs.jcim.5c00051
DO - 10.1021/acs.jcim.5c00051
M3 - Article
C2 - 40197028
AN - SCOPUS:105003943375
SN - 1549-9596
VL - 65
SP - 3990
EP - 3998
JO - Journal of Chemical Information and Modeling
JF - Journal of Chemical Information and Modeling
IS - 8
ER -