Identification and Molecular Mechanism of Novel Immunomodulatory Peptides from Gelatin Hydrolysates: Molecular Docking, Dynamic Simulation, and Cell Experiments.

The purpose of this study was to identify donkey-hide gelatin-derived immunomodulatory peptides targeting Toll-like receptor 4-myeloid differentiation 2 (TLR4-MD2) and elucidate their binding modes using physicochemical property prediction, molecular docking, molecular dynamics simulations, and in vitro cell experiments. After hydrolyzing gelatin, 519 peptides were identified by liquid chromatography-tandem mass spectrometry. Peptides VQLSGEEK and GFSGLDGAKG bound to TLR4-MD2 with high binding affinity. In TLR4-MD2, Arg90, Ser118, Phe126, Tyr131, and Arg264 were key residues involved in the binding of these peptides. The RMSD and Rg values demonstrated that VQLSGEEK-TLR4-MD2 and GFSGLDGAKG-TLR4-MD2 complexes had stable and compact conformations. VQLSGEEK and GFSGLDGAKG were found to increase the cell viability and phagocytic activity of RAW264.7 macrophages; significantly promote the production of cytokines TNF-α, IL-1ß, and IL-6 in cells; and inhibit the overproduction of nitric oxide (NO) and cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results provided preliminary evidence that VQLSGEEK and GFSGLDGAKG could function as two-way immunomodulatory peptides with immunostimulatory and anti-inflammatory activities.

Identification of Oncorhynchus mykiss nebulin-derived peptides as bitter taste receptor TAS2R14 blockers by in silico screening and molecular docking.

Human bitter taste receptor TAS2R14 (T2R14) can widely perceive bitterness, which has always been an issue for people to overcome. This study was aimed at identifying bioactive peptides obtained from Oncorhynchus mykiss nebulin hydrolysates as bitter taste receptor blockers by physicochemical property prediction, molecular docking, and in vitro determination of bitterness intensity using electronic tongue. Exploration of the interaction mechanism of these peptides with T2R14 by molecular docking models indicated that peptides ADM and ADW had high affinities for T2R14 to block the binding of bitter substances into the receptor. Addition of ADM and ADW to quinine caused reduction in bitterness intensity, with IC50 values of 420.32 ± 6.26 µM and 403.29 ± 4.10 µM, respectively. Hydrogen bond interaction and hydrophobic interaction were responsible for manifesting the high affinities of these peptides for the receptor. Residues Thr86, Asp168, and Phe247 may be the key amino acids within the binding site.

Identification of tuna protein-derived peptides as potent SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation.

The present study aimed to identify potential SARS-CoV-2 inhibitory peptides from tuna protein by virtual screening. The molecular docking was performed to elicit the interaction mechanism between targets (Mpro and ACE2) and peptides. As a result, a potential antiviral peptide EEAGGATAAQIEM (E-M) was identified. Molecular docking analysis revealed that E-M could interact with residues Thr190, Thr25, Thr26, Ala191, Leu50, Met165, Gln189, Glu166, His164, His41, Cys145, Gly143, and Asn119 of Mpro via 11 conventional hydrogen bonds, 9 carbon hydrogen bonds, and one alkyl interaction. The formation of hydrogen bonds between peptide E-M and the residues Gly143 and Gln189 of Mpro may play important roles in inhibiting the activity of Mpro. Besides, E-M could bind with the residues His34, Phe28, Thr27, Ala36, Asp355, Glu37, Gln24, Ser19, Tyr83, and Tyr41 of ACE2. Hydrogen bonds and electrostatic interactions may play vital roles in blocking the receptor ACE2 binding with SARS-CoV-2.