Advances in Molecular Docking Techniques for Targeting Protein Misfolding in Neurodegenerative Diseases

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, represent a significant global health challenge with limited therapeutic options. Protein misfolding and aggregation, a common pathological hallmark in these disorders, have emerged as promising targets for therapeutic intervention. Molecular docking techniques have played a pivotal role in the identification and design of small molecules that can modulate protein misfolding, offering new hope for effective treatments. This review provides an overview of recent advancements in molecular docking techniques for targeting protein misfolding in neurodegenerative diseases. We discuss the principles and methodologies behind molecular docking, including various scoring functions and algorithms employed for accurate ligand-protein interactions. Additionally, we explore the use of molecular dynamics simulations and machine learning approaches to enhance the precision of docking studies. Furthermore, we highlight case studies and success stories where molecular docking has contributed to the discovery of potential drug candidates for neurodegenerative diseases. These include compounds that inhibit amyloid-β aggregation in Alzheimer's disease, α-synuclein oligomerisation in Parkinson's disease, and mutant huntingtin aggregation in Huntington's disease. We also discuss the problems and restrictions of molecular docking related to neurodegenerative diseases, such as how to accurately show the flexibility of proteins and why docking results need to be confirmed by experiments. We also discuss the structural biology methods, such as cryo-electron microscopy and X-ray crystallography, and how these techniques might help in improving molecular docking studies.