Live or let die: Bcl-2 protein transmembrane domain interactions in apoptosis signalling
We investigate the interactions among the transmembrane domains of BCL-2 receptors in mitochondrial outer membrane. BCL-2 protein family is a key regulator of cell death. Thereby, the cell fate is decided by a complex network of interactions between pro- and anti-apoptotic members of the family, which govern mitochondrial outer membrane permeabilisation. Our multiscaling molecular dynamics simulations, consisting of spontaneous association of membrane-embedded transmembrane receptors at coarse-grained resolution, resolution transformation to atomistic resolution, and the refinement of the most often occurring interaction interfaces in atomistic simulations, complement the experimental investigations of Tobias Beigl and Prof. Frank Essman at the institute for clinical Pharmacology. Our joint efforts aim at shedding light on the molecular mechanisms of function of a prominent BCL-2 receptor, BOK, and its possible regulation by anti-apoptotic proteins.
Note. In order to be able to perform these simulations, Kristyna Pluhackova and Tobias Beigl have succeeded in acquiring a grant for computing time on the supercomputer HoreKa at KIT.