Berlin 2018 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 1: Protein Structure and Dynamics

BP 1.1: Hauptvortrag

Montag, 12. März 2018, 09:30–10:00, H 1028

Thermodynamics and kinetics of protein aggregation from atomistic simulations — •Birgit Strodel — Institute of Complex Systems: Structural Biochemistry, Forschungszentrum Jülich, Germany — Institute of Theoretical and Computational Chemistry, Heinrich Heine University, Düsseldorf

I will present two different techniques developed by my group, which allow the extraction of the thermodynamics and kinetics of protein aggregation from molecular dynamics data. The first technique uses transition networks (TNs) to characterize the aggregation pathways, as will be demonstrated for the formation amyloid β-protein (Aβ) oligomers, which are connected to the development of Alzheimer's disease. The TNs reveal that the oligomers leading to the size distributions observed in experiments originate from metastable compact conformations, while extended oligomers are the ones driving the aggregation process. It is further elucidated how changes in the sequence of Aβ, a pH change or the presence of Cu(II) ions lead to different aggregation pathways, which is of direct relevance to the toxicity of Aβ oligomers. In the other technique, we extended the idea of automated Markov state models (MSM) to protein self-assembly by constructing reaction coordinates from descriptors that are invariant to permutations of the molecular indexing. I will demonstrate the power of this technique for the identification of kinetically relevant aggregation pathways for the KFFE peptide. Both the TN and MSM formalism developed by us are quite general and can therefore be used for the automated analysis of any other self-assembling molecular system.