Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides
Chronic diseases, such as hypertension, cause great harm to human health. Conventional drugs have promising therapeutic effects, but also cause significant side effects. Food-sourced angiotensin-converting enzyme (ACE) inhibitory peptides are an excellent therapeutic alternative to pharmaceuticals,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Foods |
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| Online Access: | https://www.mdpi.com/2304-8158/12/8/1573 |
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| author | Mingzhe Ma Yinghui Feng Yulu Miao Qiang Shen Shuting Tang Juan Dong John Z. H. Zhang Lujia Zhang |
| author_facet | Mingzhe Ma Yinghui Feng Yulu Miao Qiang Shen Shuting Tang Juan Dong John Z. H. Zhang Lujia Zhang |
| author_sort | Mingzhe Ma |
| collection | DOAJ |
| description | Chronic diseases, such as hypertension, cause great harm to human health. Conventional drugs have promising therapeutic effects, but also cause significant side effects. Food-sourced angiotensin-converting enzyme (ACE) inhibitory peptides are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, there is no systematic and effective screening method for ACE inhibitory peptides, and the lack of understanding of the sequence characteristics and molecular mechanism of these inhibitory peptides poses a major obstacle to the development of ACE inhibitory peptides. Through systematically calculating the binding effects of 160,000 tetrapeptides with ACE by molecular docking, we found that peptides with Tyr, Phe, His, Arg, and especially Trp were the characteristic amino acids of ACE inhibitory peptides. The tetrapeptides of WWNW, WRQF, WFRV, YYWK, WWDW, and WWTY rank in the top 10 peptides exhibiting significantly high ACE inhibiting behaviors, with IC<sub>50</sub> values between 19.98 ± 8.19 μM and 36.76 ± 1.32 μM. Salt bridges, π–π stacking, π–cations, and hydrogen bonds contributed to the high binding characteristics of the inhibitors and ACE. Introducing eight Trp into rabbit skeletal muscle protein (no Trp in wide sequence) endowed the protein with a more than 90% ACE inhibition rate, further suggesting that meat with a high content of Trp could have potential utility in hypertension regulation. This study provides a clear direction for the development and screening of ACE inhibitory peptides. |
| first_indexed | 2024-03-11T05:01:56Z |
| format | Article |
| id | doaj.art-47c8383a84f5457b82dbf9e185753dc5 |
| institution | Directory Open Access Journal |
| issn | 2304-8158 |
| language | English |
| last_indexed | 2024-03-11T05:01:56Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Foods |
| spelling | doaj.art-47c8383a84f5457b82dbf9e185753dc52023-11-17T19:13:35ZengMDPI AGFoods2304-81582023-04-01128157310.3390/foods12081573Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 TetrapeptidesMingzhe Ma0Yinghui Feng1Yulu Miao2Qiang Shen3Shuting Tang4Juan Dong5John Z. H. Zhang6Lujia Zhang7Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaSchool of Food Science and Technology, Shihezi University, Shihezi 832000, ChinaSchool of Food Science and Technology, Shihezi University, Shihezi 832000, ChinaShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaChronic diseases, such as hypertension, cause great harm to human health. Conventional drugs have promising therapeutic effects, but also cause significant side effects. Food-sourced angiotensin-converting enzyme (ACE) inhibitory peptides are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, there is no systematic and effective screening method for ACE inhibitory peptides, and the lack of understanding of the sequence characteristics and molecular mechanism of these inhibitory peptides poses a major obstacle to the development of ACE inhibitory peptides. Through systematically calculating the binding effects of 160,000 tetrapeptides with ACE by molecular docking, we found that peptides with Tyr, Phe, His, Arg, and especially Trp were the characteristic amino acids of ACE inhibitory peptides. The tetrapeptides of WWNW, WRQF, WFRV, YYWK, WWDW, and WWTY rank in the top 10 peptides exhibiting significantly high ACE inhibiting behaviors, with IC<sub>50</sub> values between 19.98 ± 8.19 μM and 36.76 ± 1.32 μM. Salt bridges, π–π stacking, π–cations, and hydrogen bonds contributed to the high binding characteristics of the inhibitors and ACE. Introducing eight Trp into rabbit skeletal muscle protein (no Trp in wide sequence) endowed the protein with a more than 90% ACE inhibition rate, further suggesting that meat with a high content of Trp could have potential utility in hypertension regulation. This study provides a clear direction for the development and screening of ACE inhibitory peptides.https://www.mdpi.com/2304-8158/12/8/1573angiotensin-converting enzyme (ACE)ACE inhibitory peptidestetrapeptidesmolecular dockingmolecular dynamics simulations |
| spellingShingle | Mingzhe Ma Yinghui Feng Yulu Miao Qiang Shen Shuting Tang Juan Dong John Z. H. Zhang Lujia Zhang Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides Foods angiotensin-converting enzyme (ACE) ACE inhibitory peptides tetrapeptides molecular docking molecular dynamics simulations |
| title | Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides |
| title_full | Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides |
| title_fullStr | Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides |
| title_full_unstemmed | Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides |
| title_short | Revealing the Sequence Characteristics and Molecular Mechanisms of ACE Inhibitory Peptides by Comprehensive Characterization of 160,000 Tetrapeptides |
| title_sort | revealing the sequence characteristics and molecular mechanisms of ace inhibitory peptides by comprehensive characterization of 160 000 tetrapeptides |
| topic | angiotensin-converting enzyme (ACE) ACE inhibitory peptides tetrapeptides molecular docking molecular dynamics simulations |
| url | https://www.mdpi.com/2304-8158/12/8/1573 |
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