From Understanding the Molecular Basis of Diseases to Drug Discovery Approaches

In the Strodel lab, different simulation techniques are applied, in particular all-atom molecular dynamics (MD) simulations with the aim to unravel the bio- and physicochemistry of disease processes; special focus is put on protein aggregation diseases. In Alzheimer’s disease, it has long been the aggregation of the amyloid-β peptide into fibrillar β-sheet structures that has been seen as a hallmark of the disease. In order to develop novel therapeutic interventions, this self-assembly processes needs to be understood in more detail.

In her talk, Birgit will demonstrate how the aggregation process can be studied using MD simulations. A particular aim of the work is to elucidate the effects of various in vivo components and conditions. These comprise the presence of metal ions, oxidative stress, an acidic environment mimicking tissue inflammation, cell membrane influence, and the brain extracellular matrix on the conformational dynamics and aggregation of the amyloid-β peptide. In the second part of her talk, Birgit will provide examples for the exploitation of insight gained from MD simulations, in combination with knowledge generated from experiments by others, towards tackling drug design.
Searching also for treatments against Covid-19 Birgit will demonstrate how her lab combines virtual screening, MD simulations and in vitro testing to identifying hit molecules as starting points for lead generation.

Speaker: Prof. Dr. Birgit Strodel, Forschungszentrum Jülich and University Düsseldorf, Germany