SKM 2023 – scientific programme
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BP: Fachverband Biologische Physik
BP 3: Computational Biophysics I
BP 3.4: Talk
Monday, March 27, 2023, 10:15–10:30, BAR 0106
Resolving hierarchical interactions of proteins in phase-separated condensates by multi-scale simulations — •Lukas Stelzl1,2,3, Kumar Gaurav1,2,3, Xiaofei Ping1,2,3, Arya Changiarath Sivadasan1,2,3, René Ketting3, and Dorothee Dormann3,4 — 1Institute of Physics, JGU Mainz, Germany — 2Faculty of Biology, JGU Mainz, Germany — 3IMB Mainz, Germany — 4Institute of Molecular Physiology, JGU Main, Germany
Liquid-liquid phase separation and the resulting phase-separated condensates of proteins help to organize cellular processes in time and space. At same time, dysregulation of phase separation is implicated in the development of neurodegenerative diseases. Using particle-based multi-scale simulations we are elucidating how phase-separated condensates can provide for specific molecular recognition and thus cellular regulation and how this specificity is lost in diseases. With simulations we are elucidating how a hierarchy of interactions such as strong interactions of folded domains and weak and multivalent interactions between disordered regions of proteins determine phase behavior. With our multi-scale methods we can simulate condensates with atomic resolution and resolve molecular details of "sticker"-"sticker" interactions, their kinetics and how these provide for specific recognition and cellular function. We also show how mutations and biochemical modifications can shift the conformational equilibria of proteins and their interactions in phase-separated condensates and favor the formation of toxic aggregates in neurodegenerative diseases.