2 Master Theses: Binding affinities of intrinsically disordered proteins – GNNQQNY crystal growth and inhibition of amyloid β-protein aggregation by D-enantiomeric peptides

Jülich Research Centre (FZJ)

Jülich, Germany

Work group:

ICS-6 – Strukturbiochemie

Area of research:

Diploma & Master Thesis

Starting date:


Contract time limit:


Job description:

The Institute of Physical Biology (IPB) from the Heinrich Heine University in Düsseldorf (HHU) cooperates closely with the Institute of Complex Systems (ICS-6): Structural Biochemistry from the Research Centre Jülich GmbH (FZJ). One of the main research topics of both institutes is related to intrinsically disordered proteins, their aggregation into fibrils, and their role in various neurodegenerative diseases. In studying these topics, researchers use experimental and computational methods in order to understand in detail related biological processes. Two Master positions are available as part of collaborations between the two institutes and are located at FZJ.

Within these collaborations we aim at elucidating the thermodynamics and structural description of amyloid proteins binding to fibrils or crystals and the interaction between the amyloid β-protein and inhibitory peptides by using a combination of enhanced molecular dynamics (MD) simulations and various types of experiments. We invite two students with strong background in physics, chemistry or biochemistry and computational skills to explore interesting scientific problems and learn state of the art MD simulation methods within the following topics:

Topic 1: GNNQQNY fibril and crystal growthThe goal of this project is to study the energetics and thermodynamics of fibril and crystal growth, and to identify the determinants for the asymmetrical crystal shape as well as the molecular groups and interactions involved. The student will calculate the binding affinity for fibril and crystal growth of a short peptide with sequence GNNQQNY from the SUP35 yeast protein. This will be achieved by deriving free energy profiles using various atomistic MD simulations techniques such as umbrella sampling, replica exchange and the weighted histogram analysis method. UV-Vis spectroscopy experiments will complement the computational methods to provide a complete picture of the aggregation and crystallization processes.

Topic 2: Inhibition of amyloid β-protein aggregation by D-enantiomeric protein aggregation and toxicityThe aim of this project is to study the interaction between the amyloid β-protein and various Denantiomeric peptides used as inhibitors for the amyloid β-protein aggregation. Currently, there ar eseveral D-peptides in clinical trials as drugs against the Alzheimer’s disease. While these peptides are very effective against the formation of toxic amyloid assemblies, the inhibition mechanism and the molecular interactions responsible are still not understood. The master student will perform extensive atomistic MD simulations in order to derive binding affinities between the the amyloid β- protein and different D-enantiomeric peptides. These quantities will be directly compared with equivalent experimental values and key molecular interactions involved will be identified from the simulations.

Please apply via recruiter’s website.

Quote Reference: 2019M-094