RTG 2450

P5: A Multiscale Treatment of Kinase Function

The figure illustrates the phosphoryl reaction and conformational changes that occur in the kinase function.Fathia Idiris, partly recreated from Wang, C. et al.; Mechanistic Insights Revealed by the Crystal Structure of a Histidine Kinase with Signal Transducer and Sensor Domains. PLoS Biol 2013, 11 (2), e1001493. https://doi.org/10.1371/journal.pbio.1001493.

The function of enzymes relies on a delicately balanced interplay of molecular motions and chemical reactions. Typical computational studies, however, struggle to describe this coupled motion and chemical reaction. Instead one focuses typically either on a quantum-chemical description of the chemical reaction, which is computationally too demanding to also treat the motion, or on the investigation of large-scale conformational motions by molecular dynamics, which cannot access chemical reactions. We aim to develop a framework that allows for swapping and coupling both approaches. As model systems, we explore kinases, which often fulfill critical biochemical tasks in catalysis or signaling.