In Vitro and In Silico Study on the Molecular Encapsulation of α-Tocopherol in a Large-Ring Cyclodextrin.

α-tocopherol is the physiologically most active form of vitamin E, with numerous biological activities, such as significant antioxidant activity, anticancer capabilities, and anti-aging properties. However, its low water solubility has limited its potential use in the food, cosmetic, and pharmaceutical industries. One possible strategy for addressing this issue is the use of a supramolecular complex with large-ring cyclodextrins (LR-CDs). In this study, the phase solubility of the CD26/α-tocopherol complex was investigated to assess the possible ratios between host and guest in the solution phase. Next, the host-guest association of the CD26/α-tocopherol complex at different ratios of 1:2, 1:4, 1:6, 2:1, 4:1, and 6:1 was studied by all-atom molecular dynamics (MD) simulations. At 1:2 ratio, two α-tocopherol units interact spontaneously with CD26, forming an inclusion complex, as supported by the experimental data. In the 2:1 ratio, a single α-tocopherol unit was encapsulated by two CD26 molecules. In comparison, increasing the number of α-tocopherol or CD26 molecules above two led to self-aggregation and consequently limited the solubility of α-tocopherol. The computational and experimental results indicate that a 1:2 ratio could be the most suitable stoichiometry to use in the CD26/α-tocopherol complex to improve α-tocopherol solubility and stability in inclusion complex formation.

Computer-Aided Virtual Screening and In Vitro Validation of Biomimetic Tyrosinase Inhibitory Peptides from Abalone Peptidome.

Hyperpigmentation is a medical and cosmetic problem caused by an excess accumulation of melanin or the overexpression of the enzyme tyrosinase, leading to several skin disorders, i.e., freckles, melasma, and skin cancer. Tyrosinase is a key enzyme in melanogenesis and thus a target for reducing melanin production. Although abalone is a good source of bioactive peptides that have been used for several properties including depigmentation, the available information on the anti-tyrosinase property of abalone peptides remains insufficient. This study investigated the anti-tyrosinase properties of Haliotis diversicolor tyrosinase inhibitory peptides (hdTIPs) based on mushroom tyrosinase, cellular tyrosinase, and melanin content assays. The binding conformation between peptides and tyrosinase was also examined by molecular docking and dynamics study. KNN1 showed a high potent inhibitory effect on mushroom tyrosinase with an IC50 of 70.83 µM. Moreover, our selected hdTIPs could inhibit melanin production through the reductions in tyrosinase activity and reactive oxygen species (ROS) levels by enhancing the antioxidative enzymes. RF1 showed the highest activity on both cellular tyrosinase inhibition and ROS reduction. leading to the lower melanin content in B16F10 murine melanoma cells. Accordingly, it can be assumed that our selected peptides exhibited high potential in medical cosmetology applications.

Prediction of the Glass Transition Temperature in Polyethylene Terephthalate/Polyethylene Vanillate (PET/PEV) Blends: A Molecular Dynamics Study.

Polyethylene terephthalate (PET) is one of the most common polymers used in industries. However, its accumulation in the environment is a health risk to humans and animals. Polyethylene vanillate (PEV) is a bio-based material with topological, mechanical, and thermal properties similar to PET, allowing it to be used as a PET replacement or blending material. This study aimed to investigate some structural and dynamical properties as well as the estimated glass transition temperature (Tg) of PET/PEV blended polymers by molecular dynamics (MD) simulations with an all-atom force field model. Four blended systems of PET/PEV with different composition ratios (4/1, 3/2, 2/3, and 1/4) were investigated and compared to the parent polymers, PET and PEV. The results show that the polymers with all blended ratios have Tg values around 344-347 K, which are not significantly different from each other and are close to the Tg of PET at 345 K. Among all the ratios, the 3/2 blended polymer showed the highest number of contacting atoms and possible hydrogen bonds between the two chain types. Moreover, the radial distribution results suggested the proper interactions in this system, which indicates that this is the most suitable ratio model for further experimental studies of the PET/PEV polymer blend.

All-Atom Molecular Dynamics Simulations on a Single Chain of PET and PEV Polymers.

Polyethylene vanillic (PEV), a bio-based material, has mechanical and thermal properties similar to polyethylene terephthalate (PET), the most common polymer used in industries. The present study aimed to investigate and compare their structural dynamics and physical data using a computational approach. The simple model of a single-chain polymer containing 100 repeating units was performed by all-atom molecular dynamics (MD) simulations with refined OPLS-AA force field parameters. As a result, the flexibility of the PEV structure was greater than that of PET. PET and PEV polymers had the predicted glass transition temperature Tg values of approximately 345 K and 353 K, respectively. PEV showed a slightly higher Tg than PET, consistent with current experimental evidence.

Computer-Aided Screening for Potential Coronavirus 3-Chymotrypsin-like Protease (3CLpro) Inhibitory Peptides from Putative Hemp Seed Trypsinized Peptidome.

To control the COVID-19 pandemic, antivirals that specifically target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently required. The 3-chymotrypsin-like protease (3CLpro) is a promising drug target since it functions as a catalytic dyad in hydrolyzing polyprotein during the viral life cycle. Bioactive peptides, especially food-derived peptides, have a variety of functional activities, including antiviral activity, and also have a potential therapeutic effect against COVID-19. In this study, the hemp seed trypsinized peptidome was subjected to computer-aided screening against the 3CLpro of SARS-CoV-2. Using predictive trypsinized products of the five major proteins in hemp seed (i.e., edestin 1, edestin 2, edestin 3, albumin, and vicilin), the putative hydrolyzed peptidome was established and used as the input dataset. To select the Cannabis sativa antiviral peptides (csAVPs), a predictive bioinformatic analysis was performed by three webserver screening programs: iAMPpred, AVPpred, and Meta-iAVP. The amino acid composition profile comparison was performed by COPid to screen for the non-toxic and non-allergenic candidates, ToxinPred and AllerTOP and AllergenFP, respectively. GalaxyPepDock and HPEPDOCK were employed to perform the molecular docking of all selected csAVPs to the 3CLpro of SARS-CoV-2. Only the top docking-scored candidate (csAVP4) was further analyzed by molecular dynamics simulation for 150 nanoseconds. Molecular docking and molecular dynamics revealed the potential ability and stability of csAVP4 to inhibit the 3CLpro catalytic domain with hydrogen bond formation in domain 2 with short bonding distances. In addition, these top ten candidate bioactive peptides contained hydrophilic amino acid residues and exhibited a positive net charge. We hope that our results may guide the future development of alternative therapeutics against COVID-19.

Rosmarinic Acid as a Potent Influenza Neuraminidase Inhibitor: In Vitro and In Silico Study.

BACKGROUND: Neuraminidase (NA), a major glycoprotein found on the surface of the influenza virus, is an important target for the prophylaxis and treatment of influenza virus infections. Recently, several plant-derived polyphenols, especially caffeic acid analogs, have been reported to exert the inhibitory activity against NA. OBJECTIVE: Herein, we aimed to investigate the anti-influenza NA activity of caffeic acid and its hydroxycinnamate analogues, rosmarinic acid and salvianolic acid A, in comparison to a known NA inhibitor, oseltamivir. METHODS: In vitro MUNANA-based NA inhibitory assay was used to evaluate the inhibitory activity of the three interested hydroxycinnamic compounds towards the influenza NA enzyme. Subsequently, allatom molecular dynamics (MD) simulations and binding free energy calculations were employed to elucidate the structural insights into the protein-ligand complexations. RESULTS: Rosmarinic acid showed the highest inhibitory activity against NA with the IC50 of 0.40 µM compared to caffeic acid (IC50 of 0.81 µM) and salvianolic acid A (IC50 of >1 µM). From 100-ns MD simulations, the binding affinity, hot-spot residues, and H-bond formations of rosmarinic acid/NA complex were higher than those of caffeic acid/NA model, in which their molecular complexations was driven mainly by electrostatic attractions and H-bond formations from several charged residues (R118, E119, D151, R152, E227, E277, and R371). Notably, the two hydroxyl groups on both phenyl and phenylacetic rings of rosmarinic acid play a crucial role in stabilizing NA through a strongly formed Hbond( s). CONCLUSION: Our findings shed light on the potentiality of rosmarinic acid as a lead compound for further development of a potential influenza NA inhibitor.