title: What are the ideal properties for functional food peptides with antihypertensive effect? A computational peptidology approach.
abstract: Peptides with antihypertensive potency have long been attractive to the medical and food communities. However, serving as food additives, rather than therapeutic agents, peptides should have a good taste. In the present study, we explore the intrinsic relationship between the angiotensin I-converting enzyme (ACE) inhibition and bitterness of short peptides in the framework of computational peptidology, attempting to find out the appropriate properties for functional food peptides with satisfactory bioactivities. As might be expected, quantitative structure-activity relationship modeling reveals a significant positive correlation between the ACE inhibition and bitterness of dipeptides, but this correlation is quite modest for tripeptides and, particularly, tetrapeptides. Moreover, quantum mechanics/molecular mechanics analysis of the structural basis and energetic profile involved in ACE-peptide complexes unravels that peptides of up to 4 amino acids long are sufficient to have efficient binding to ACE, and more additional residues do not bring with substantial enhance in their ACE-binding affinity and, thus, antihypertensive capability. All of above, it is coming together to suggest that the tripeptides and tetrapeptides could be considered as ideal candidates for seeking potential functional food additives with both high antihypertensive activity and low bitterness.
authors.affiliation: Center of Bioinformatics (COBI), School of Life Science and Technology, University of Electronic Science and Technology of China (UESTC), Chengdu 610054, China. p_zhou@uestc.edu.cn
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Ren
authors.forename: Congcong
authors.initials: C
authors.lastname: Wang
authors.forename: Feifei
authors.initials: F
authors.lastname: Tian
mesh_terms: D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods*; D055951:Functional Food / Q000032:analysis*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010455:Peptides
keywords: ACE; BPPb; Bioactivity; Computational peptidology; Functional food; HBP; ONIOM; PB/SA; PCA; PLS; Peptide; Poisson–Boltzmann/surface area; QM/MM; QSAR; RAS; SVM; angiotensin I-converting enzyme; high blood pressure; our own N-layered integrated molecular orbital and molecular mechanics; partial least squares; principal component analysis; quantitative structure–activity relationship; quantum mechanics/molecular mechanics; radykinin potentiating peptide; renin-angiotensin system; support vector machine