PhD defence by Erik van Dijk




The role of hydrophobicity in protein folding and aggregation

Erik van Dijk

Prof. Dr. Jaap Heringa

Faculty of Science


PhD conferral


The interaction of hydrophobic (water-fearing) amino acids with water (the hydrophobic effect) plays a crucial role in protein folding and aggregation. Aggregation of proteins is believed to be the cause of Alzheimer's and Parkinson's disease. The aggregation process takes years under physiological conditions, making it hard to study in the laboratory. One of the solutions used to study aggregation on reasonable time scales, is to perform the experiments at high temperatures (60 °C), increasing the speed of the reaction.


Theoretical and computational methods are necessary to translate the experimental results back to physiological conditions. The contribution of the hydrophobic effect to protein folding and aggregation changes with temperature, complicating the translation from experimental results to consequences for the biological process. In this thesis the temperature dependence of the hydrophobic effect is investigated in three steps. 


In the first step, we estimate the temperature dependence of the interactions using a theoretical and statistical approach, and find that both approaches produce roughly the same results. In the second step, we introduce the temperature dependence of hydrophobic particles in an established computational model and determine the parameter ranges that reproduce known experimental results. In the third step, we verify that the estimates of the temperature dependence are consistent with the parameter ranges that reproduce experimental results, and use these parameters to make predictions for the thermodynamic properties of real proteins.