Comparative Analysis of Protein Misfolding in Neurodegenerative Diseases Using Evaluation based on the Distance from Average Solution (EDAS) Method

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, have emerged as major public health concerns due to their debilitating effects on cognition and motor function. A common pathological feature underlying these disorders is the aggregation and misfolding of specific proteins within the central nervous system. Investigating the molecular mechanisms of protein misfolding is crucial to understanding disease progression and developing potential therapeutic interventions. In this study, we explore the utility of the Enhanced Dissipative Particle Dynamics (EDAS) method in simulating the conformational changes and misfiling behaviour of proteins associated with neurodegenerative diseases. The EDAS method is a robust and efficient computational approach that integrates principles from classical molecular dynamics with dissipative particle dynamics to capture the dynamics of protein folding and aggregation at the mesoscale level. By employing this novel method, we gain insight into the structural stability and interactions of amyloidogenic proteins, including amyloid-beta (Aβ) in Alzheimer's, alpha-synuclein in Parkinson's, and huntingtin in Huntington's disease. Through extensive EDAS simulations, we analyse the kinetic and thermodynamic aspects of protein misfiling, unravelling the pivotal role of specific molecular events in initiating and propagating misfolding cascades. EDAS simulations provide a valuable tool for elucidating the underlying mechanisms of neurodegenerative diseases and contribute to the development of rational drug design aimed at halting or delaying disease progression. The diseases under consideration are Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and prion diseases. The aspects to be evaluated are the Degree of Protein Misfolding, Therapeutic Options, Disease Prevalence, and Disease Progression Rate. Parkinson's Disease is got first rank and Multiple Sclerosis is got lowest rank.