Author(s) :

Yash Jaju, Divya Ramamoorthy.

Volume/Issue :

Abstract :

Affecting hundreds of thousands of people around the world, Huntington’s Disease is a neurodegenerative disorder causing involuntary movements, poor-decision making, nervous system shutdown, and ultimately death. The aim of this project was to identify molecules as inhibitors to limit the disease-causing mutation, known as mHTT (mutant huntingtin). We used the PDB 4FEB in this study. Three groups of compounds, 50 CNS (central nervous system) compounds, 13 mHTT inhibitors, and 50 peptidomimetics that we screened in the study. In addition, we analyzed the binding site and created a docking grid to prepare the mHTT protein for SP (standard precision) and XP (extra precision) docking. We also performed QikProp analysis, which gave us the log BB, molMW, and Percent Human Oral Absorption of the ligand. Finally, we created ligand interaction diagrams between the top-performing ligands and the 4FEB chain to demonstrate the key interactions. Top-scoring ligands were selected based on their docking scores, with acceptable scores ranging from -3 to -4.5 after XP Docking. While the two top-scoring compounds showed strong computational binding efficiency, in vitro testing is required to ensure the compounds execute effectively as they did computationally. Going forward, our goal is to continue researching and computationally docking ligands that can drive the design of new compounds for effectively targeting the mHTT protein in silico.