Effects of in vivo conditions on amyloid-βaggregation: computational approaches

Amyloid aggregation has been extensively studied in vitro under conditions that are far from the physiological ones. There is need to extend these investigations to in vivo conditions where amyloid formation is affected by a myriad of biochemical interactions. The aim of my work is to elucidate the effects of various in vivo components and conditions, such as the presence of Cu2+, oxidative stress, an acidic environment mimicking brain inflammation, but also the sheer existence of the neuronal cell membrane on the conformational dynamics and aggregation of the amyloid-βpeptide (Aβ) that is strongly related to the development of Alzheimer’s disease. To this end, we perform large-scale molecular dynamics simulations and develop novel analysis tools allowing us to unravel the amyloid aggregation pathways under varying external conditions. The most recent and enlightening results from these simulations will be presented in my talk.