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Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Related Experiment Video

Updated: Mar 21, 2026

Folding and Characterization of a Bio-responsive Robot from DNA Origami
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DeepIM: Integrating Channel-Spatial Attention with Transformer for DNA i-Motif Folding Status Prediction.

Rui Wu1,2, Hui Zhang1, Li-Rong Zhang3

  • 1School of Electronic Information Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010021, China.

Journal of Chemical Information and Modeling
|March 19, 2026
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Summary

DeepIM, a new deep learning model, accurately predicts i-motif (iM) DNA folding. This advancement aids in understanding gene regulation and cancer development by analyzing complex DNA structures.

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Area of Science:

  • Genomics and Bioinformatics
  • Computational Biology
  • Molecular Biology

Background:

  • i-Motifs (iM) are crucial DNA structures involved in gene regulation, telomere stability, and cancer.
  • Experimental detection methods for iMs are costly and low-throughput.
  • Existing computational models fail to capture intricate DNA sequence-structure relationships for iM formation.

Purpose of the Study:

  • To develop a novel deep learning model, DeepIM, for accurate and interpretable prediction of i-motif folding status.
  • To overcome limitations of traditional experimental and computational methods in iM detection.
  • To enhance understanding of sequence-structure relationships in DNA secondary structures.

Main Methods:

  • DeepIM utilizes a Transformer architecture with a channel-spatial attention (CSA) mechanism.
  • DNA sequences are encoded into k-mers with embedding and positional encoding.
  • CSA mechanism extracts local features (C-tracts, flanking regions) and Transformer models long-range dependencies.

Main Results:

  • DeepIM achieved 92.6% accuracy in predicting iM folding status, surpassing XGBoost (86.0%), random forest (87.0%), and iM-Seeker (90.3%).
  • The model demonstrated strong cross-cell-line generalization capabilities.
  • Attention weight analysis identified distinctive iM sequence patterns, validating model interpretability.

Conclusions:

  • DeepIM represents a significant advancement in DNA secondary structure prediction using deep learning.
  • The model offers a highly accurate and interpretable method for analyzing i-motif formation.
  • DeepIM facilitates a deeper understanding of the complex sequence-structure interplay in DNA, with implications for gene regulation and disease research.