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Casein-Derived Peptides with Antihypertensive Potential: Production, Identification and Assessment of Complex Formation with Angiotensin I-Converting Enzyme (ACE) through Molecular Docking Studies

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Abstract

Hypertension is nowadays one of the major world concerns in public health. Several food proteins, among which caseins, can be substrates for generating peptides with antihypertensive potential. With the increasingly evolution of computational tools, in silico molecular modeling have gained prominence in studies of protein-ligand complexes in different research fields, such as pharmaceutics and biochemical engineering. However, the application of such methodologies in food-related research can be considered still embryonic. Thus, the central aim of the present work was to apply molecular modelling in order to elucidate the molecular bases of the anti-hypertensive potential of milk caseins-derived peptides. Firstly, hydrolysates obtained from a controlled trypsinolysis of caseins were fractioned according to their molecular weight, by ultrafiltration and RP-HPLC. The obtained fractions were evaluated with regard to their in vitro inhibitory angiotensin-converting enzyme activity (%IACE). Six chromatographic fractions were identified, and three of them displayed high ACE-inhibition (F1: 80.68%; F2: 79.00%; and F4: 62.44%). Finally, intermolecular interactions networks in complexes formed between ACE and the identified peptides were assessed through in silico molecular docking. At the molecular level, a correlation between in vitro and in silico results was found: the peptides FFVAPFPEVFGK (F6), FALPQYLK (F2, F4) and ALNEINQFYQK (F1) presented the lowest biding energies and interacted by specific H-bonds, electrostatic and hydrophobic interactions formed within ACE active site S1 residues (Ala354, Glu384, and Tyr 523) and the Zn2+ coordinated residues (His383, His387, and Glu411). The fraction F3, despite its low total peptide concentration, presented a moderate inhibitory activity for ACE (49.2%), likely due to H-bonds between HQGLPQEVLNENLLR and the active site S1 residues.

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Acknowledgements

We are grateful to BIOAGRO-UFV, NuBioMol-UFV and UFV Computational Cluster for providing the facilities for carrying out the experiments, and to Brazilian agencies CAPES, CNPq, FAPEMIG, FINEP, FUNARBE and SisNANO/MCTI, for the financial support. Ms. M.R. Oliveira and Ms. T.J. Silva are especially grateful to CNPq for their scholarships.

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Author notes

  1. Thomás Valente De Oliveira and Marcelo Depólo Polêto contributed equally to this work.

Authors and Affiliations

  1. Departamento de Tecnologia de Alimentos, Universidade Federal de Viçosa, Campus Universitário, s/n, CEP, Viçosa, MG, 36570-900, Brazil

    Thomás Valente De Oliveira, Mara Rose De Oliveira, Thaís Jordânia Silva, Monique Renon Eller, Jane Sélia dos Reis Coimbra & Eduardo Basílio De Oliveira

  2. Grupo de Bioinformática Estrutural, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, Porto Alegre, RS, Brazil

    Marcelo Depólo Polêto

  3. Departamento de Biologia Geral, Universidade Federal de Viçosa, Campus Universitário, s/n, CEP, Viçosa, MG, 36570-900, Brazil

    Marcelo Depólo Polêto

  4. Núcleo de Análise de Biomoléculas, Universidade Federal de Viçosa, Campus Universitário, CEP, Viçosa, MG, 36570-900, Brazil

    Edvaldo Barros

  5. Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Campus Universitário, s/n, CEP, Viçosa, MG, 36570-900, Brazil

    Valéria Monteze Guimarães & Maria Cristina Baracat-Pereira

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  1. Thomás Valente De Oliveira
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  9. Jane Sélia dos Reis Coimbra
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Correspondence to Thomás Valente De Oliveira or Eduardo Basílio De Oliveira.

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De Oliveira, T.V., Polêto, M.D., De Oliveira, M.R. et al. Casein-Derived Peptides with Antihypertensive Potential: Production, Identification and Assessment of Complex Formation with Angiotensin I-Converting Enzyme (ACE) through Molecular Docking Studies. Food Biophysics 15, 162–172 (2020). https://doi.org/10.1007/s11483-019-09616-9

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