ElfLab MD store
||ElfLab MD store|
||SNIC Small Storage|
||Malin Lüking <email@example.com>|
||2022-07-07 – 2023-08-01|
DNA-binding proteins (DBPs) are crucial for life. They protect and repair and regulate the genome on demand and therefore resource-efficiently. It is of fundamental interest to understand how proteins bind their target sites fast and accurately. In our research we use a combination of fluorescent microscopy and molecular modelling to answer this question. It has long been argued that hydrogen bonds between protein side chains and base edges in the final complex dictate specificity (Milo and Phillips 2015) but structural and kinetic data shows increasingly that there are more contributors to sequence specificity (Hammar et al. 2012; Marklund et al. 2020). We measure on- and off-rates between a DBP and thousands of sequences on a microarray (Marklund et al., 2021). We can follow the formation and the breakage of interactions as well as the protein and DNA conformations during non-specific binding, target site recognition and formation of the specific complex in restraint and metadynamics simulations. Obtaining enough sampling of this transition will allow us to validate the simulations against the experiments.