Informatics Approach Towards Targeting HTR1B Pathways in Neuropharmacology for Migraine Treatment

Introduction: Migraine is a prevalent and debilitating neurological disorder, with current therapies often being ineffective and causing side effects. Recent studies in neuropharmacology present the serotonin 1B receptor (HTR1B) as a viable avenue of migraine treatment since it influences pain and vasoconstriction. Methods: This research broadly uses computational approaches to explain the 5-hydroxytryptamine receptor 1B (HTR1B) pathways in neuropharmacology for migraine treatment. Text mining results reveal 25 essential genes, and network pharmacology provides complex mechanisms among genes and proteins, revealing a sophisticated network consisting of 41 nodes and 361 edges. The protein structure and function were elucidated through high-resolution protein modeling and validation, yielding significant new information. The structure has a resolution of 2.05 Å and a C-score of 0.30. The virtual screening explored the best ligands, which had binding affinities ranging from -13.8 to -9.6 kcal/mol from a set of 25 molecules. Docking results indicated that FDA-approved ligands showed high binding affinities, ranging from -11.4 to -12.5 kcal/mol among other natural and synthetic libraries. The pharmacokinetic profiles of the potential drugs showed significant diversity in their solubility and lipophilicity qualities (F(2,6) = 15.13, p = 0.004), suggesting different levels of safety and efficacy. MD simulation clarified the dynamic interactions between the protein and ligand at 100ns. Results: The RMSD values were stable within the 6.0-7.5 Å range, indicating a consistent structure. RMSF values revealed areas of flexibility in the protein. The toxicity risk assessment of Xaliproden indicated modest risks. Conclusion: This study provides a foundation for targeted HTR1B-based migraine therapies and highlights the value of informatics tools in accelerating drug discovery in neuropharmacology.