Effects of in vivo conditions on protein aggregation: computational approaches

Birgit Strodel

Birgit Strodel

Computational Biochemistry Group, Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Foschungszentrum Jülich, 52425 Jülich, Germany

Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany

The aggregation of proteins into β-sheet structures 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 protein aggregation is affected by a myriad of biochemical interactions. As a hallmark of numerous diseases, these self-assembly processes need to be understood in detail to develop novel therapeutic interventions. The aim of our work is to elucidate the effects of various in vivo components and conditions, such as the presence of metal ions, oxidative stress, an acidic environment mimicking tissue inflammation, the presence of cell membranes and the brain extracellular matrix on the conformational dynamics and aggregation of the Alzheimer’s disease-related amyloid-β peptide. To this end, we develop multiscale simulation approaches, perform large-scale molecular dynamics simulations, and establish novel analysis tools allowing us to unravel the aggregation pathways under varying external conditions. The most recent and enlightening results from these simulations will be presented in my talk.

 

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