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introductionVitamin D plays a crucial role in maintaining muscle and bone health and has been increasingly implicated in neurological disorders, including depression and anxiety, which are conditions closely associated with dysregulation of the serotonin 1A receptor (5-HT1A receptor). This study employs molecular modeling techniques to investigate the potential agonistic activity of Vitamin D on the 5-HT1A receptor. Additionally, it seeks to elucidate the key structural motifs and molecular interactions that underline the binding affinity between Vitamin D and the receptor. The insights gained from this research may inform the design of Vitamin D-derived compounds with optimized pharmacological profiles, contributing to therapeutic advancements in related neurological conditions.

methodsWe selected five structures of the 5-HT1A receptor (PDB IDs: 7E2Y, 7E2Z, 8W8B, 8JSP, and 8JT6) for Protein-Ligand Interaction Fingerprint (PLIF) analysis. We conducted molecular docking to evaluate the binding efficiency of two forms of Vitamin D, ergocalciferol and cholecalciferol, to the 5-HT1A receptor. Following this, we performed Molecular Dynamics (MD) simulations to assess the stability of these interactions. RESULTS AND DISCUSSION: Docking results revealed binding energies below -6.64 kcal/mol for both forms of Vitamin D, with ergocalciferol achieving a maximum binding energy of -7.78 kcal/mol. ASP116 emerged as a pivotal residue in stabilizing these interactions. MD simulations indicated that the Vitamin D-5-HT1A complexes exhibited stability comparable to the serotonin-bound 5-HT1A receptor complex.

conclusionOur study suggests that Vitamin D may function as an agonist for the 5-HT1A receptor, with ASP116 playing a critical role in binding. Yet, further