Browsing by Author "Tuntufye, Edna"

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Anti-Aging Potential of Vitamin D: An Insilico Study
(NM-AIST, 2025-02) Tuntufye, Edna
Despite extensive studies on the impact of vitamin D in aging retardation, the detailed atomic- level binding interactions between vitamin D (D2 and D3 forms) and associated anti-aging proteins have been largely unexplored. The study investigates these interactions by using molecular docking techniques to provide deeper insights into how vitamin D affects the structural dynamics and stability of the proteins associated with anti-aging process. The docking results reveal that vitamin D interacts most favorably with Sirt1 (PDB ID: 4zzi), a crucial anti-aging protein involved in DNA repair and metabolic regulation. Docking studies, including blind, grid, and hydrated docking approaches, show that vitamin D2 binds more strongly than vitamin D3 across all receptors evaluated. Specifically, in blind docking, vitamin D2 exhibited a binding affinity of −37.99 kJ/mol, while vitamin D3 showed a binding affinity of −34.85 kJ/mol. Grid docking revealed a similar trend, with vitamin D2 demonstrating a higher binding affinity of −41.38 kJ/mol compared to −40.08 kJ/mol for vitamin D3. These interactions are primarily hydrophobic, involving key residues such as Val445, Phe273, and Ala262 which form alkyl and pi-alkyl interactions with the ligands. The introduction of water molecules in hydrated docking further enhanced binding affinity, with vitamin D2 achieving an average binding free energy of −48.33 kJ/mol and vitamin D3 −45.94 kJ/mol highlighting the stabilizing effect of water in ligand-protein interactions. The Sirt1-vitamin D complexes maintained stable structural integrity with minimal RMSD and Rg fluctuations. The free energy surface revealed two preferred conformations for vitamin D2 and one for vitamin D3 indicating greater conformational flexibility for vitamin D2. The MM-PBSA results indicated that the vitamin D3-Sirt1 complex demonstrated superior stability, with a binding free energy of −167.12 ± 16.35 kJ/mol, compared to the vitamin D2-Sirt1 complex (−144.07±19.45). This suggests that vitamin D3 might have a more stable interaction with Sirt1, potentially offering enhanced therapeutic efficacy. The structural analysis revealed that both forms of vitamin D exhibited similar binding modes with vitamin D3 interacting at a lower energy than vitamin D2. These findings offer crucial insights into the molecular mechanisms underlying the role of vitamin D in aging, revealing key differences between vitamin D2 and D3 binding to Sirt1.
In Silico Analysis of Vitamin D Interactions with Aging Proteins: Docking, Molecular Dynamics, and Solvation Free Energy Studies
(MDPI, 2024-10-11) Tuntufye, Edna; Paul, Lucas; Raymond, Jofrey; Chacha, Musa; Paluch, Andrew; Shadrack, Daniel
Aging is a natural process that is also influenced by some factors like the food someone eats, lifestyle decisions, and impacts on general health. Despite the recognized role of nutrition in modulating the molecular and cellular mechanisms underlying aging, there is a lack of comprehensive exploration into potential interventions that can effectively mitigate these effects. In this study, we investigated the potential anti-aging properties of vitamin D by examining its interactions with key molecular targets involved in aging-related pathways. By using molecular docking and dynamics techniques, we evaluate the interactions and stability of vitamins D2 and D3 with key proteins involved in aging pathways, such as SIRT1, mTOR, AMPK, Klotho, AhR, and MAPK. Our results reveal promising binding affinities between vitamin D and SIRT1 forms, with energy values of −48.33 kJ/mol and −45.94 kJ/mol for vitamins D2 and D3, respectively, in aqueous environments. Moreover, molecular dynamics simulations revealed that the vitamin D3–SIRT1 complex exhibited greater stability compared with the vitamin D2–SIRT1 complex. The study calculated the solvation free energy to compare the solubility of vitamins D2 and D3 in water and various organic solvents. Despite their strong interactions with water, both vitamins exhibited low solubility, primarily due to the high energy cost associated with cavity formation in the aqueous environment. Compared with other solvents, water demonstrated particularly low solubility for both vitamins. This suggested that vitamins D2 and D3 preferred binding to aging receptors over dissolving in bulk aqueous environments, supporting their strong therapeutic interactions with these receptors. These findings shed light on the molecular mechanisms underlying vitamin D’s potential anti-aging effects and lay the groundwork for developing nutraceuticals targeting aging and associated diseases. Understanding these mechanisms holds promise for future interventions aimed at promoting healthy aging and enhancing overall well-being.