Quantum Chemical, Spectroscopic and In Silico (Molecular Docking, Molecular Dynamic and <scp>ADME</scp> ) Studies on Anti‐Aging Pentapeptide‐3 (Vialox)

ABSTRACT Skin aging is accelerated by environmental factors such as long‐term UV exposure, stress, smoking, alcohol consumption, and a poor diet. This process primarily results from the build up of oxidative stress caused by reactive oxygen species (ROS). Pollutants, toxins, and excessive exposure to ultraviolet A (UVA) radiation trigger the production of ROS. Common visible signs of skin aging, including wrinkles, spots, fine lines, and loss of moisture and elasticity, serve as both indicators and targets for treating skin aging. Anti‐aging peptides have been extensively researched for their potential to prevent skin aging, maintain skin health, and reduce ROS due to their unique properties, including low molecular weight, modifiability, and minimal bioaccumulation. These peptides, known as cosmeceutical peptides, can interact with signaling pathways and receptors that play a crucial role in the skin aging process. Their ability to influence these mechanisms of aging is an important area of ongoing research in the field of skin treatment. Pentapeptide‐3 (Vialox) has the sequence Gly‐Pro‐Arg‐Pro‐Ala and is derived from snake venom. It functions as an antagonist of the acetylcholine receptor, safely blocking the release of sodium ions at the synaptic membrane of muscles. This action prevents muscles from contracting as frequently, leading to muscle relaxation. This article attempts to investigate the potential interactions of Pentapeptide‐3, a synthetic peptide, with Transforming Growth Factor‐β receptor‐1 (TGF‐β receptor‐1), Tumor necrosis factor‐α (TNF‐α), Mitogen‐Activated Protein Kinase 14 (MAPK14), and RAC‐alpha serine/threonine‐protein kinase (AKT‐1) signaling pathways, which are the targets of anti‐aging activities with in silico approaches. The geometric optimization, theoretical vibrational wavenumbers, HOMO‐LUMO, and MEP analyses were performed using the DFT method and the 6‐31++G(d,p) basis set to describe and understand their electronic structure and reactive sites of Pentapeptide‐3. A Potential Energy Distribution (PED) analysis was conducted to elucidate fundamental vibrational wavenumbers and their assignments. By comparing the theoretical and experimental wavenumbers from FTIR, ATR‐FTIR, and Raman spectra, appropriate wavenumber assignments were also determined for each amino acid residue in the Pentapeptide‐3 sequence. The molecular interactions of Pentapeptide‐3 with various receptors that are important in skin aging were also explored using in silico methods, including molecular docking and molecular dynamics analysis. The molecular docking results revealed binding energies of −8.12 kcal/mol for (TGF‐β receptor‐I) and −8.25 kcal/mol for MAPK14. Additionally, molecular dynamics studies were conducted for 50 and 100 ns, indicating that Pentapeptide‐3 remained stable in the active sites of both receptors. Theoretical, experimental, and in silico studies suggest that Pentapeptide‐3 is a promising candidate for preventing and treating skin aging.