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April 20th 2019

Scientists from the University of Twente have captured the aggregation of proteins in a computational model. The aggregation occurs in the brain of patients with Parkinson's disease or Alzheimer's disease. Now that the proteins have been captured in the model the researchers hope they can gain a better understanding of how these diseases arise.

The rising life expectancy in Western society has led to an increase in age-related conditions such as Parkinson's disease and Alzheimer's disease. In both of these diseases protein aggregation occurs in the patient's brain. Interestingly, these protein aggregates are folded into specific, so-called cross-β-sheet structures.

Why does aggregation occur?
The scientists Ioana Ilie, Wouter den Otter and Wim Briels from the University of Twente are investigating why the proteins aggregate in this manner and which conditions accelerate or delay this process. Using models and simulations the researchers want to identify the basic principles underlying Parkinson's disease and Alzheimer's disease.

Simulation in three steps
Simulating and modelling the aggregation is a complex process. No off-the-shelf computer programs are available because the aggregation takes too long and it involves large molecules. The researchers therefore developed their own model and simulation of the proces. That was realised in several steps. First of all they simplified the protein into a short chain of five particles. These particles can assume different shapes: spherical for chaotic segments and cylindrical for folded segments. The interactions between particles can change accordingly: weak and isotropic in the chaotic state, strong and anisotropic for the folded states. Secondly they simulated the movements of the particles. And thirdly the physicists ensured that the particles could respond to each other. The parameters of the model were based as much as possible on experiments.

Simulation successful
When they ran the simulation the researchers saw that the particles did indeed spontaneously aggregate. First of all small aggregations or short threads arose and then the threads continued to grow. The researchers will now further refine their protein model using experimental results from the other groups in this programme.

Further information
Rotational Brownian Dynamics simulations of clathrin cage formation, I.M. Ilie, W.K. den Otter and W.J. Briels, J. Chem. Phys. 141, 065101 (2014).