RESUMEN
The aggregation of amyloid fibrils can lead to various diseases including Alzheimer's, Parkinson's disease, and transmissible spongiform encephalopathy. Amyloid fibrils can develop from a variety of proteins in the body as they misfold into a primarily ß-sheet structure and aggregate. Human lysozyme has been shown to have far reaching effects in the human health-a homologous enzyme, hen egg-white lysozyme, has been shown to denature to a primarily ß-sheet structure at low pH and high alcohol content solution. We have studied these systems in atomic-level detail with a combination of constant pH and microsecond long molecular dynamics simulation in explicit solvent, which cumulatively total over 10 µs of simulation time. These studies have allowed us to determine two potential unfolding pathways depending on the protonation state of a key glutamic acid residue as well as the effect of solution dynamics and pH on the unfolding process.