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

• DOI: 10.1007/s11483-019-09616-9
• Publication Date: 2019-11-27T19:03:40Z
• Authors: Thomás Valente De...; Marcelo Depólo Po...; Mara Rose De Oliv...; Thaís Jordânia Silva; Edvaldo Barros; Valéria Monteze G...; Maria Cristina Ba...; Monique Renon Eller; Jane Sélia dos Re...; Eduardo Basílio D...
• Keywords: 0106 biological sciences; 01 natural sciences; 3. Good health

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.