Applying Viral Nanoparticles in a Treatment Vector for Alzheimer’s Disease Using Molecular Dynamics Simulations

Akshata Rudrapatna

A progressively neurodegenerative disease, Alzheimer’s disease presents a serious emotional and physical cost to patients and their families today. In industrialized countries, the increasing overall age of the population creates a large group of people at risk for Alzheimer’s disease, so it is imperative that a cure is developed soon. However, new treatments are often too large in size to cross the blood-brain barrier (BBB) and thus do not localize to regions of the brain well. Nanoparticles offer one potential solution to this problem. The extremely small size and high targeting accuracy of nanoparticle vectors allow them to deliver therapeutic molecules to a treatment site without compromising surrounding tissue . . . In this project, solvated models of the cowpea mosaic virus (CPMV) capsid were developed to identify its possible therapeutic values in Alzheimer’s disease. Using molecular dynamics simulations, the CPMV capsid proteins were shown to interact with a combination of tight-junction protein ZO-2 (a BBB protein) and vimentin (a protein found in Alzheimer’s plaques); a combination of tight-junction protein ZO-2, vimentin, occludin, and vinculin (two other BBB proteins); vimentin alone; and a combination of vimentin and beta-amyloid (another protein found in Alzheimer’s plaques), without overheating the systems. A Ramachandran plot and contact maps were used respectively to verify the secondary structure of the CPMV capsid proteins and location of interactions within the molecular systems.