Structural and Functional Profiling of Huntington’s Disease Proteins and Molecular Docking of Novel Therapeutic Candidates

Abstract

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by CAG repeat expansion in the huntingtin gene, leading to mutant protein aggregation and neuronal dysfunction. This study focuses on comprehensive structural and functional profiling of HD-associated proteins combined with molecular docking of selected therapeutic candidates. Protein sequence analysis, domain characterization, and three-dimensional structural modeling were performed to identify aggregation-prone regions and functional motifs. Structural validation ensured stereochemical reliability prior to docking simulations. A library of candidate small molecules was screened computationally to evaluate interaction patterns within critical protein domains implicated in aggregation and neurotoxicity. Binding-site prediction, interaction mapping, and stability assessment were incorporated to explore potential modulation of pathogenic conformations. The objective is to establish a computational framework for identifying molecules capable of influencing protein aggregation dynamics and functional disruption in HD. This in silico approach provides a foundation for subsequent in vitro validation and rational therapeutic design targeting neurodegenerative proteinopathies.