Deducing Underlying Mechanisms from Protein Recruitment Data

Abstract

By using fluorescent labelling techniques, the distribution and dynamics of proteins can be measured within living cells, allowing to study in vivo the response of cells to a triggering event, such as DNA damage. In order to evaluate the reaction rate constants and to identify the proteins and reactions that are essential for the investigated process, mechanistic models are used, which often contain many proteins and associated parameters and are therefore underdetermined by the data. In order to establish criteria for assessing the significance of a model, we present here a systematic investigation of the information that can be reliably deduced from protein recruitment data, assuming that the complete set of reactions that affect the data of the considered protein species is not known. To this purpose, we study in detail models where one or two proteins that influence each other are recruited to a substrate. We show that in many cases the kind of interaction between the proteins can be deduced by analyzing the shape of the recruitment curves of one protein. Furthermore, we discuss in general in which cases it is possible to discriminate between different models and in which cases it is impossible based on the data. Finally, we argue that if different models fit experimental data equally well, conducting experiments with different protein concentrations would allow discrimination between the alternative models in many cases. © 2013 Lengert, Drossel.