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A novel Angiotensin-I-converting enzyme (ACE) inhibitory peptide IAF (Ile-Ala-Phe) from pumpkin seed proteins: in silico screening, inhibitory activity, and molecular mechanisms

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Abstract

Pumpkin seed proteins with desirable nutritional properties have attracted great interest as an innovative source of bioactive peptides with beneficial effects in recent years. The current study aimed to screen novel ACE inhibitory peptides from pumpkin seed proteins by in silico approach and further elucidate the underlying inhibition mechanisms. A novel tripeptide, IAF (Ile-Ala-Phe) with acceptable bioavailability properties exhibited considerable ACE inhibitory ability with an IC50 of 19.87 ± 0.50 μM. Molecular docking study showed that IAF could bound with key residues in the active site of ACE. Further molecular dynamics (MD) simulation suggested that the simulation systems reached equilibrium after 5 ns and that ACE and IAF can form complex in stabilization. Moreover, MD analysis revealed that the hydrogen bonds interactions between IAF and two key residues (His513 and Glu162) of ACE and the chelation between O3 atom of IAF and Zn2+ play more important roles in the stabilization for ACE–IAF complex, which might contribute significantly to the ACE inhibitory activity. Our study indicated that the novel and potential ACE inhibitory peptide IAF from pumpkin seed proteins can be considered as a promising candidate for controlling hypertension.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ADME:

Absorption, distribution, metabolism, and elimination

FAPGG:

N-[3-(2-furyl)acryloyl]-Phe-Gly-Gly

LINCS:

Linear constraint solver

MD:

Molecular dynamic

MOE:

Molecular operating environment

PME:

Particle mesh Ewald

RMSD:

Root mean square deviation

RMSF:

Root mean square fluctuation

Rg:

Radius of gyration

SASA:

Solvent-accessible surface area

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Funding

This work was supported by [National Natural Science Foundation of China] (Grant number 32001702).

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Authors and Affiliations

  1. College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, 210023, Jiangsu, China

    Fuqiang Liang, Yumeng Shi, Jiayi Shi, Tai Zhang & Ran Zhang

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  1. Fuqiang Liang
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  2. Yumeng Shi
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  3. Jiayi Shi
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  4. Tai Zhang
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  5. Ran Zhang
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Correspondence to Fuqiang Liang.

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Liang, F., Shi, Y., Shi, J. et al. A novel Angiotensin-I-converting enzyme (ACE) inhibitory peptide IAF (Ile-Ala-Phe) from pumpkin seed proteins: in silico screening, inhibitory activity, and molecular mechanisms. Eur Food Res Technol 247, 2227–2237 (2021). https://doi.org/10.1007/s00217-021-03783-1

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