Modelling Proteasome Dynamics In A Bayesian Framework

Sabine Stübler compares different proteasome isoforms and subtypes in terms of their transport and active site-related parameters applying an existing computational model. In a second step, the author extends this model to be able to describe the influence of proteasome inhibitors in in vitro experiments. The computational model, which describes the hydrolysis of short fluorogenic peptides by the 20S proteasome, is calibrated to experimental data from different proteasome isoforms using an approximate Bayesian computation approach. The dynamics of proteasome inhibitors are included into the model in order to demonstrate how to modulate the inhibitor’s transport parameters for strong or isoform-specific inhibition.