Systems biology approaches to macromolecules: the role of dynamic protein assemblies in information processing

Macromolecular protein assemblies govern many cellular processes and are disturbed in many diseases including cancer. Often seen as static molecular machines, protein complexes involved in signal transduction networks exhibit intricate dynamics that are critical for their function. Using the RAS-RAF-MEK-ERK pathway as example we discuss recent progress in our understanding of protein complex dynamics achieved through mathematical modelling, computational simulations and structural studies. The emerging picture highlights that both spatial and temporal dynamics cooperate to enable correct signal processing and the fine tuning of timing, duration and strengths of signalling. These dynamic processes are subverted by oncogenic mutations and contribute to tumorigenesis and drug resistance.