Phenolic-protein interactions: insight from in-silico analyses – a review

Abstract

Phenolic compounds are ubiquitous plant secondary metabolites that possess various biological activities and are known to interact with proteins, altering their structure and properties. Therefore, interactions between these compounds and proteins has gained increasing attention due to their potential benefits to human health and for exploitation by the food industry. Phenolic compounds and proteins can form complexes via covalent linkages and/or non-covalent interactions through hydrophobic, electrostatic, van der Waals forces and hydrogen bonding. This review describes possible mechanisms of phenol-protein complex formation, their physiological action and activities that are important in the food industry, and possible outcomes in the terms of molecular docking and simulation analysis. The conformational changes of the protein upon binding with polyphenols can lead to the folding or unfolding of the protein molecules, forming insoluble or soluble complexes. The concentration of polyphenols, their molecular weight and structure, ions/cofactors and conditions of the system determine the precipitation or solubilization of the complex, affecting their nutritional and functional properties as well as their bioactivities. In this regard, molecular docking and simulation studies of phenolic-protein interactions allows comprehensive virtual screening of competitive/non-competitive and site-specific/non-specific conjugation of phenolics with different protein targets and facilitates understanding the observed effects. The docking analysis of flavonoids with enzymes and milk proteins has indicated their potential application in producing nutraceuticals and functional foods. Thus, combining molecular docking and simulation studies with experimental techniques is vital for better understanding the reactions that take place during digestion to engineer and manufacture novel food ingredients with desirable pharmacological properties and as potential food additives. Graphical Abstract

Bioaccessibility of Rosmarinic Acid and Basil (Ocimum basilicum L.) Co-Compounds in a Simulated Digestion Model—The Influence of the Endogenous Plant Matrix, Dose of Administration and Physicochemical and Biochemical Digestion Environment

“…It has been reported that, on the one hand, the action of biochemical factors can facilitate compound release from the physical food matrix structure and complexes with its macromolecular components; on the other hand, complexation with digestion enzymes may decrease the content of free compounds [ 25 , 31 , 32 ]. Presumably, the limited effect of biochemical factors on bioaccessibility found in this study was connected with the specific character of the applied phytochemicals subjected to digestion.…”

Potential Utilization of Phenolic Acid Compounds as Anti-Inflammatory Agents through TNF-α Convertase Inhibition Mechanisms: A Network Pharmacology, Docking, and Molecular Dynamics Approach

“…The effects of phenolic acid compounds on protein rigidity provide a deeper understanding of the inhibitory mechanism at the structural level. Stabilization of the protein–ligand complex and subsequent decrease in protein rigidity provide compelling evidence for the disruption of the normal function of the enzyme by phenolic acid compounds . TNF-α convertase inhibition has emerged as a potential strategy for anti-inflammation due to its crucial role in regulating inflammatory processes.…”

Covalent polyphenols-proteins interactions in food processing: formation mechanisms, quantification methods, bioactive effects, and applications

“…Scientists have achieved much progress in strengthening and clarifying the formation of polyphenol-protein covalent complexes through prevalent utilization of molecular docking for predicting phenolic compounds and protein binding sites ( 136 ). However, limited research has been conducted on comprehensively determining the binding sites and identifying the specific amino acid residues that directly contribute to the formation of polyphenol-protein covalent complexes.…”