AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Food Science and Human Wellness Article
PDF (1.7 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Structural requirements and interaction mechanisms of ACE inhibitory peptides: molecular simulation and thermodynamics studies on LAPYK and its modified peptides

Biying Zhanga,b, Jingbo Liua, Hedi Wena, Feng Jianga, Erlei Wanga, Ting Zhanga( )
Jilin Provincial Key Laboratory of Nutrition and Functional Food, College of Food Science and Engineering, Jilin University, Changchun 130062, China
College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China

Peer review under responsibility of KeAi Communications Co., Ltd.

Show Author Information

Abstract

The understanding of the structural requirements and the intermolecular-interaction mechanism are important for discovering potent angiotensin-converting enzyme (ACE) inhibitory peptides. In this study, we modified an egg-white derived peptide, LAPYK, using the amino acids with different properties to produce the LAPYK-modified peptides. The ACE inhibitory activities of the modified peptides were determined to explore the structural requirements of ACE inhibitory peptides (ACEIPs). Molecular simulation and isothermal titration calorimetry analysis were used to investigate interactions between the peptides and ACE. We found that hydrophobicity and the amino acids with ring structures were beneficial for the ACE inhibitory activities of the peptides. The results of the molecular mechanics poisson boltzmann surface area (MMPBSA) binding free energy calculations indicated that the polar solvation free energy (ΔGpolar) of the charged peptides (LAPYK, LAPYE) were unfavorable for binding to ACE. On the other hand, the results of isothermal titration calorimetry analyses suggested that the enthalpy-driven ACE-peptide interactions were more favorable than the entropy-driven ACE-peptide interaction counterparts.

Keywords

Molecular dynamics simulationMolecular dockingACE inhibitory peptidesIsothermal titration calorimetry

References

[1]

R. Natesh, S.L.U. Schwager, E.D. Sturrock, et al., Crystal structure of the human angiotensin-converting enzyme-lisinopril complex, Nature 421(6922) (2003) 551-554. http://doi.org/10.1038/nature01370.
Crossref Google Scholar
[2]

A. Iwaniak, P. Minkiewicz, M. Darewicz, Food-originating ACE inhibitors, including antihypertensive peptides, as preventive food components in blood pressure reduction, Compr. Rev. Food Sci. Food Saf. 13(2) (2014) 114-134. http://doi.org/10.1111/1541-4337.12051.
Crossref Google Scholar
[3]

B. Rubin, M.J. Antonaccio, M.E. Goldberg, et al., Chronic antihypertensive effects of captopril (SQ 14,225), an orally active angiotensin Ⅰ-converting enzyme inhibitor, in conscious 2-kidney renal hypertensive rats, Eur. J. Pharmacol. 51(4) (1978) 377-388. http://doi.org/10.1016/0014-2999(78)90429-6.
Crossref Google Scholar
[4]

B.E. Karlberg, F. Fyhrquist. C. Gronhagen-Riska, et al., Enalapril and lisinopril in renovascular hypertension-antihypertensive and hormonal effects of two new angiotensin-converting-enzyme (ACE) inhibitors. A preliminary report, Scand. J. Urol. Nephrol. 79 (1984) 103-106.
Crossref Google Scholar
[5]

S.J. Rho, J.S. Lee, Y.I. Chung, et al., Purification and identification of an angiotensin Ⅰ-converting enzyme inhibitory peptide from fermented soybean extract, Process Biochem. 44(4) (2009) 490-493. http://doi.org/10.1016/j.procbio.2008.12.017.
Crossref Google Scholar
[6]

H.F. Ge, Z.Z. Cai, J.L. Chai, et al., Egg white peptides ameliorate dextran sulfate sodium-induced acute colitis symptoms by inhibiting the production of pro-inflammatory cytokines and modulation of gut microbiota composition, Food Chem. 360 (2021) 129981. https://doi.org/10.1016/j.foodchem.2021.129981.
Crossref Google Scholar
[7]

C. Liu, J.B. Liu, M.Q. Wang, et al., Construction and application of membrane-bound angiotensin-I converting enzyme system: a new approach for the evaluation of angiotensin-I converting enzyme inhibitory peptides, J. Agric. Food Chem. 68(20) (2020) 5723-5731. http://doi.org/10.1021/acs.jafc.9b08082.
Crossref Google Scholar
[8]

M. Tu, X. Qiao, C. Wang, et al., In vitro and in silico analysis of dual-function peptides derived from casein hydrolysate, Food Sci. Hum. Well. 10(1) (2021) 32-37. http://doi.org/10.1016/j.fshw.2020.08.014.
Crossref Google Scholar
[9]

Z.F. Bhat, S. Kumar, H.F. Bhat, Antihypertensive peptides of animal origin: a review, Crit. Rev. Food Sci. Nutr. 57(3) (2017) 566-578. http://doi.org/10.1080/10408398.2014.898241.
Crossref Google Scholar
[10]

C. Daskaya-Dikmen, A. Yucetepe, F. Karbancioglu-Guler, et al., Angiotensin-I-converting enzyme (ACE)-inhibitory peptides from plants, Nutrients 9(4) (2017) 316. http://doi.org/10.3390/nu9040316.
Crossref Google Scholar
[11]

J.P. Wu, R.E. Aluko, S. Nakai, Structural requirements of angiotensin Ⅰ-converting enzyme inhibitory peptides: quantitative structure-activity relationship study of di- and tripeptides, J. Agric. Food Chem. 54(3) (2006) 732-738. http://doi.org/10.1021/jf051263l.
Crossref Google Scholar
[12]

X. Guan, J. Liu, QSAR study of angiotensin Ⅰ-converting enzyme inhibitory peptides using SVHEHS descriptor and OSC-SVM, Int. J. Pept. Res. Ther. 25(1) (2018) 247-256. http://doi.org/10.1007/s10989-017-9661-x.
Crossref Google Scholar
[13]

M. Shu, X.M. Cheng, Y.R. Zhang, et al., Predicting the activity of ACE inhibitory peptides with a novel mode of pseudo amino acid composition, Pro. Pept. Lett. 18(12) (2011) 1233-1243. http://doi.org/ 10.2174/092986611797642706.
Crossref Google Scholar
[14]

M. Liu, M. Du, Y.C. Zhang, et al., Purification and identification of an ACE inhibitory peptide from walnut protein, J. Agric. Food Chem. 61(17) (2013) 4097-4100. http://doi.org/10.1021/jf4001378.
Crossref Google Scholar
[15]

T. Ma, Q. Fu, Q. Mei, et al., Extraction optimization and screening of angiotensin-converting enzyme inhibitory peptides from Channa striatus through bioaffinity ultrafiltration coupled with LC-Orbitrap-MS/MS and molecular docking, Food Chem. 354 (2021) 129589-129589. http://doi.org/10.1016/j.foodchem.2021.129589.
Crossref Google Scholar
[16]

Z. Yu, H. Guo, D. Shiuan, et al., Interaction mechanism of egg white- derived ACE inhibitory peptide TNGIIR with ACE and its effect on the expression of ACE and AT1 receptor, Food Sci. Hum. Well. 9(1) (2020) 52-57. http://doi.org/10.1016/j.fshw.2019.12.009.
Crossref Google Scholar
[17]

Y. Fan, Z. Yu, W. Zhao, et al., Identification and molecular mechanism of angiotensin-converting enzyme inhibitory peptides from Larimichthys crocea titin, Food Sci. Hum. Well. 9(3) (2020) 257-263. http://doi.org/10.1016/j.fshw.2020.04.001.
Crossref Google Scholar
[18]

O. Sercinoglu, P. Ozbek, gRINN: a tool for calculation of residue interaction energies and protein energy network analysis of molecular dynamics simulations, Nucleic Acids Res. 46(W1) (2018) W554-W562. http://doi.org/10.1093/nar/gky381.
Crossref Google Scholar
[19]

S.M. Nayeem, E.M. Sohail, G.P. Sudhir, et al., Computational and theoretical exploration for clinical suitability of Remdesivir drug to SARS-CoV-2, Eur. J. Pharmacol. 890 (2021) 173642. http://doi.org/Artn17364210.1016/J.Ejphar.2020.173642.
Crossref Google Scholar
[20]
D. Sahu, M. Bastidas, C.W. Lawrence, et al., Assessing coupled protein folding and binding through temperature-dependent isothermal titration calorimetry, in: Methods in Enzymology, Elsevier, 2016, pp. 23-45.
Crossref
[21]

O.D. Monera, T.J. Sereda, N.E. Zhou, et al., Relationship of sidechain hydrophobicity and α-helical propensity on the stability of the single‐stranded amphipathic α-helix, J. Pept. Sci. 1(5) (1995) 319-329.
Crossref Google Scholar
[22]

M. Ángel Sentandreu, F. Toldrá, A fluorescence-based protocol for quantifying angiotensin-converting enzyme activity, Nat. Protoc. 1(5) (2006) 2423-2427. http://doi.org/10.1038/nprot.2006.349.
Crossref Google Scholar
[23]

G.M. Morris, R. Huey, W. Lindstrom, et al., AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility, J. Comput. Chem. 30(16) (2009) 2785-2791. http://doi.org/10.1002/jcc.21256.
Crossref Google Scholar
[24]

B.Y. Zhang, J.B. Liu, C. Liu, et al., Bifunctional peptides with antioxidant and angiotensin-converting enzyme inhibitory activity in vitro from egg white hydrolysates, J. Food Biochem. 44(9) (2020) e13347. http://doi.org/ARTNe1334710.1111/jfbc.13347.
Crossref Google Scholar
[25]

M.J. Abraham, T. Murtola, R. Schulz, et al., GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX 1-2 (2015) 19-25. http://doi.org/10.1016/j.softx.2015.06.001.
Crossref Google Scholar
[26]

B. Hess, P-LINCS: a parallel linear constraint solver for molecular simulation, J. Chem. Theory Comput. 4(1) (2008) 116-122. http://doi.org/10.1021/ct700200b.
Crossref Google Scholar
[27]

T. Darden, D. York, L. Pedersen, Particle mesh Ewald_ An N·log(N) method for Ewald sums in large systems, J. Chem. Phys. 98(12) (1993) 10089-10092. http://doi.org/10.1063/1.46439710.1063/1.470043.
Crossref Google Scholar
[28]

Hoover, Canonical dynamics: equilibrium phase-space distributions, Phys. Rev. 31(3) (1985) 1695-1697. http://doi.org/10.1103/PhysRevA.31.1695.
Crossref Google Scholar
[29]

A.R.M. Parrinello, Polymorphic transitions in single crystals: a new molecular dynamics method, J. Appl. Phys. 52 (1981) 7182-7190. http://doi.org/10.1063/1.32869310.1063/1.2121687.
Crossref Google Scholar
[30]

A.H. Pripp, T. Isaksson, L. Stepaniak, et al., Quantitative structure-activity relationship modelling of ACE-inhibitory peptides derived from milk proteins, Eur. Food Res. Technol. 219(6) (2004) 579-583. http://doi.org/10.1007/s00217-004-1004-4.
Crossref Google Scholar
[31]

A. Aleman, B. Gimenez, E. Perez-Santin, et al., Contribution of Leu and Hyp residues to antioxidant and ACE-inhibitory activities of peptide sequences isolated from squid gelatin hydrolysate, Food Chem. 125(2) (2011) 334-341. http://doi.org/10.1016/j.foodchem.2010.08.058.
Crossref Google Scholar
[32]

A. Nuchprapha, S. Paisansak, P. Sangtanoo, et al., Two novel ACE inhibitory peptides isolated from longan seeds: purification, inhibitory kinetics and mechanisms, RSC Adv. 10(22) (2020) 12711-12720. http://doi.org/10.1039/d0ra00093k.
Crossref Google Scholar
[33]

R. He, H. Ma, W. Zhao, et al., Modeling the QSAR of ACE-inhibitory peptides with ANN and its applied illustration, Int. J. Pept. 2012 (2012) 620609-620609. http://doi.org/10.1155/2012/620609.
Crossref Google Scholar
[34]

R.E. Aluko, Structure and function of plant protein-derived antihypertensive peptides, Curr. Opin. Food Sci. 4 (2015) 44-50. http://doi.org/10.1016/j.cofs.2015.05.002.
Crossref Google Scholar
[35]

M. Mirzaei, S. Mirdamadi, M. Safavi, et al., The stability of antioxidant and ACE-inhibitory peptides as influenced by peptide sequences, LWT-Food Sci. Technol. 130 (2020) 109710. http://doi.org/10.1016/j.lwt.2020.109710.
Crossref Google Scholar
[36]

N. Yasunori, Y. Naoyuki, S. Kumi, et al., Purification and characterization of angiotensin Ⅰ-converting enzyme inhibitors from sour milk, J. Dairy Sci. 78(4) (1995) 777-783.
Crossref Google Scholar
[37]

M.F. Sanner, Python: a programming language for software integration and development, J. Mol. Graphics. 17(1) (1999) 57-61.
Google Scholar
[38]

H. Ni, L. Li, G. Liu, et al., Inhibition mechanism and model of an angiotensin Ⅰ-converting enzyme (ACE)-inhibitory hexapeptide from Yeast (Saccharomyces cerevisiae), PLoS ONE 7(5) (2012) e37077. http://doi.org/ARTN e3707710.1371/journal.pone.0037077.
Crossref Google Scholar
[39]

V.K. Jimsheena, L.R. Gowda, Arachin derived peptides as selective angiotensin Ⅰ-converting enzyme (ACE) inhibitors: structure-activity relationship, Peptides 31(6) (2010) 1165-1176. http://doi.org/10.1016/j.peptides.2010.02.022.
Crossref Google Scholar
[40]

O. Abdelhedi, R. Nasri, L. Mora, et al., In silico analysis and molecular docking study of angiotensin Ⅰ-converting enzyme inhibitory peptides from smooth-hound viscera protein hydrolysates fractionated by ultrafiltration, Food Chem. 239 (2018) 453-463. http://doi.org/10.1016/j.foodchem.2017.06.112.
Crossref Google Scholar
[41]

Z.Q. Xu, C.P. Wu, D.X. Sun-Waterhouse, et al., Identification of post-digestion angiotensin-I converting enzyme (ACE) inhibitory peptides from soybean protein isolate: their production conditions and in silico molecular docking with ACE, Food Chem. 345 (2021) 128855. http://doi.org/ARTN12885510.1016/j.foodchem.2020.128855.
Crossref Google Scholar
[42]

O. Abdelhedi, R. Nasri, M. Jridi, et al., In silico analysis and antihypertensive effect of ACE-inhibitory peptides from smooth-hound viscera protein hydrolysate: enzyme-peptide interaction study using molecular docking simulation, Process Biochem. 58 (2017) 145-159. http://doi.org/10.1016/j.procbio.2017.04.032.
Crossref Google Scholar
[43]

L. Fang, M. Geng, C. Liu, et al., Structural and molecular basis of angiotensin-converting enzyme by computational modeling: insights into the mechanisms of different inhibitors, PLoS ONE 14(4) (2019) e0215609. http://doi.org/10.1371/journal.pone.0215609.
Crossref Google Scholar
[44]

M. Gasset, G.R.C. Pereira, B.D.A.A. Vieira, et al., Comprehensive in silico analysis and molecular dynamics of the superoxide dismutase 1 (SOD1) variants related to amyotrophic lateral sclerosis, PLoS ONE 16(2) (2021) e0247841. http://doi.org/10.1371/journal.pone.0247841.
Crossref Google Scholar
[45]

E. Fuglebakk, J. Echave, N. Reuter, Measuring and comparing structural fluctuation patterns in large protein datasets, Bioinformatics 28(19) (2012) 2431-2440. http://doi.org/10.1093/bioinformatics/bts445.
Crossref Google Scholar
[46]

P. Bhatt, T. Joshi, K. Bhatt, et al., Binding interaction of glyphosate with glyphosate oxidoreductase and C-P lyase: molecular docking and molecular dynamics simulation studies, J. Hazard. Mater. 409 (2021) 124927. http://doi.org/ARTN12492710.1016/j.jhazmat.2020.124927.
Crossref Google Scholar
[47]

S. Wan, A.P. Bhati, S.J. Zasada, et al., Rapid, accurate, precise and reproducible ligand-protein binding free energy prediction, Interface Focus 10(6) (2020) 20200007. http://doi.org/10.1098/rsfs.2020.0007.
Crossref Google Scholar
[48]

J. Sharma, V. Kumar Bhardwaj, R. Singh, et al., An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against non structural protein-15 of SARS-CoV-2, Food Chem. 346 (2021) 128933. http://doi.org/10.1016/j.foodchem.2020.128933.
Crossref Google Scholar
[49]

X. Lan, L. Sun, Y. Muhammad, et al., Studies on the interaction between angiotensin-converting enzyme (ACE) and ACE inhibitory peptide from Saurida elongata, J. Agric. Food Chem. 66(51) (2018) 13414-13422. http://doi.org/10.1021/acs.jafc.8b04303.
Crossref Google Scholar
[50]

N. Deng, P. Zhang, P. Cieplak, et al., Elucidating the energetics of entropically driven protein-ligand association: calculations of absolute binding free energy and entropy, J. Phys. Chem. B 115(41) (2011) 11902-11910. http://doi.org/10.1021/jp204047b.
Crossref Google Scholar
[51]

J. Wu, D. Xie, X. Chen, et al., Inhibitory mechanism of a substrate-type angiotensin Ⅰ-converting enzyme inhibitory peptide, Process Biochem. 79 (2019) 97-104. http://doi.org/10.1016/j.procbio.2018.12.018.
Crossref Google Scholar
Food Science and Human Wellness
Volume 11 Issue 6,
November 2022
Pages 1623-1630
DOI: 10.1016/j.fshw.2022.06.021
Cite this article:
Zhang B, Liu J, Wen H, et al. Structural requirements and interaction mechanisms of ACE inhibitory peptides: molecular simulation and thermodynamics studies on LAPYK and its modified peptides. Food Science and Human Wellness, 2022, 11(6): 1623-1630. https://doi.org/10.1016/j.fshw.2022.06.021

610

Views

31

Downloads

27

Crossref

26

Web of Science

30

Scopus

0

CSCD

Altmetrics
Received: 22 June 2021
Revised: 13 August 2021
Accepted: 18 October 2021
Published: 18 July 2022
© 2022 Beijing Academy of Food Sciences.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return