Towards quantitative prediction of proteasomal digestion patterns of proteins

We discuss the problem of proteasomal degradation of proteins. Though proteasomes are important for all aspects of cellular metabolism, some details of the physical mechanism of the process remain unknown. We introduce a stochastic model of the proteasomal degradation of proteins, which accounts for the protein translocation and the topology of the positioning of cleavage centers of a proteasome from first principles. For this model we develop a mathematical description based on a master equation and techniques for reconstruction of the cleavage specificity inherent to proteins and the proteasomal translocation rates, which are a property of the proteasome species, from mass spectroscopy data on digestion patterns. With these properties determined, one can quantitatively predict digestion patterns for new experimental set-ups. Additionally we design an experimental set-up for a synthetic polypeptide with a periodic sequence of amino acids, which enables especially reliable determination of translocation rates.