An integrated De novo sequencing and virtual screening strategy for the discovery of low-abundance natural peptides with potential bioactivities from Asini Corii Colla

peer-reviewed · Journal of Chromatography B · 2026

peer-reviewed · Journal of Chromatography B · 2026. Han Zhang et al. Purpose Natural bioactive peptides in animal-derived traditional medicines are characterized by their low…
Date 2026-10-01
Type peer-reviewed
Venue Journal of Chromatography B
Publisher Elsevier BV
Contribution downstream-application
DOI 10.1016/j.jchromb.2026.125321

Abstract

Purpose Natural bioactive peptides in animal-derived traditional medicines are characterized by their low abundance and high biological activity and have attracted increasing attention from researchers in recent years. However, the effective discovery of these peptides remains challenging due to several factors, including limited protein database coverage, relatively low accuracy of protein identification, and difficulties in obtaining individual peptide monomers. In this study, using Asini Corii Colla (ACC) as the research vehicle, we aimed to establish an integrated analytical strategy for discovering low-abundance natural peptides with potential bioactivities by integrating high-coverage identification with bioactivity prediction. Methods Natural peptides of ACC was analyzed using nano-liquid chromatography-tandem mass spectrometry (NanoLC-MS/MS). The de novo sequencing algorithm was used for high-coverage analysis of natural peptides. Potential bioactive peptides were screened using bioinformatics tools such as Peptide Ranker, and bioactivity predictions were further performed against the BIOPEP-UWM database to preliminarily obtain candidate bioactive peptides and their possible functional targets. Molecular docking was subsequently employed to evaluate the binding affinity between the candidate peptides and their targets. Results A total of 4764 natural peptides from ACC were identified by de novo sequencing. Peptide Ranker screened out 152 potential bioactive peptides with scores greater than 0.50. After further evaluation of water solubility, stability, safety, and absorbability, 39 peptides were prioritized as advantageous candidates. Search results from the BIOPEP-UWM database suggested that 39 peptides contained sequence features associated with reported ACE- and DPP-IV-inhibitory peptides. Molecular docking simulations showed that five peptides could form energetically favorable binding conformations with both ACE and DPP-IV, implying their theoretical potential for ACE- and DPP-IV inhibition. Conclusion This study established a strategy for the discovery of low-abundance natural peptides with potential bioactivities. The study preliminarily characterized the natural peptide profile of ACC and identified candidate peptides with potential dual antihypertensive and antidiabetic activities, thereby providing foundational data for exploring the material basis underlying the blood-pressure-regulating and blood-glucose-modulating effects of ACC.

Authors

  1. Han Zhang · Beijing University of Chinese Medicine
  2. Xiwang Li · Beijing University of Chinese Medicine
  3. Siqi Wang · Beijing University of Chinese Medicine
  4. Shouqi Zhang · Beijing University of Chinese Medicine
  5. Gan Luo · Beijing University of Chinese Medicine
  6. Xiaoyan Gao · Beijing University of Chinese Medicine

Methods and tools

  • Asini Corii Colla bioactive peptides: De novo sequences 4764 natural peptides from Asini Corii Colla (donkey-hide gelatin, Ejiao), a traditional Chinese medicine, then screens them in silico (Peptide Ranker, BIOPEP-UWM, docking) down to five candidate dual ACE and DPP-IV inhibitors.

Methods it uses

  • PEAKS: Commercial DP-based de novo

Cites (6)

Seen in the charts

Back to the full map

Back to top