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

Abstract

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.

TIPred: a novel stacked ensemble approach for the accelerated discovery of tyrosinase inhibitory peptides

“…According to the molecular docking simulation experiments, the distance in the hydrogen bond between E2–12 and tyrosinase structures was 1.5–3.3 Å, implying that E2–12 could be deemed as a moderately strong covalent interaction [ 54 ]. Similar to the analyzed results of abalone biomimetic peptides (hdTIPs) [ 43 ], the cationic amino acid residues (Arg20, 38, 95, 268, 321) of the catalytic domain on tyrosinase seems to be the key binding target of E2–12 and other hempseed TIPs. These results indicate that the peptide E2–12 as derived from this study could be a promising TIP.…”

“…After that, the molecular docking approach was used to assess the ability of the selected TIPs to bind to the active site of the tyrosinase enzyme. Specifically, the molecular docking between the selected TIPs and the polyphenol oxidase domain (chains A–D) of the crystal structure of mushroom tyrosinase from Agaricus bisporus (PDB: 2Y9X) was performed using two protein-peptide docking web servers, namely [ 43 ] GalaxyPepDock ( http://galaxy.seoklab.org/pepdock ) and HPEPDOCK ( http://huanglab.phys.hust.edu.cn/hpepdock/ ). The GalaxyPepDock server was used to conduct the template-based molecular docking simulation, while the HPEPDOCK server was used to estimate the template-free (global) molecular docking scores.…”

Application of Molecular Dynamics Simulations to Determine Interactions between Canary Seed (Phalaris canariensis L.) Bioactive Peptides and Skin-Aging Enzymes

“…To gain insights into antioxidant activities of the bioactive peptide fraction (F-VI), the deep learning-based AnOxPePred algorithm was applied to calculate the probability of a particular sequence to present antioxidant, free radical scavenger, or quenching activities [30]. Other studies have also successfully applied AnOxPePred as a tool to predict antioxidant bioactivity of abalone [31] and egg [32] peptides. In these studies, the antioxidant scores predicted by AnOxPePred of several peptides correlated with their antioxidant activity evaluated by in vitro chemical [32] and cellular assays [31].…”

“…Other studies have also successfully applied AnOxPePred as a tool to predict antioxidant bioactivity of abalone [31] and egg [32] peptides. In these studies, the antioxidant scores predicted by AnOxPePred of several peptides correlated with their antioxidant activity evaluated by in vitro chemical [32] and cellular assays [31].…”

RING 4.0: faster residue interaction networks with novel interaction types across over 35,000 different chemical structures

“…Structural ensemble analysis is one of the main applications of RING. It is commonly used to analyze molecular dynamics simulations by calculating probabilistic contact networks ( 12 , 13 ), and to analyze protein stability and perform virtual screening ( 14 , 15 ).…”