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BP: Fachverband Biologische Physik

BP 15: Computational Biophysics III

BP 15.3: Vortrag

Mittwoch, 11. März 2026, 10:00–10:15, BAR/SCHÖ

Multiscale Simulation of Phosphofructokinase-1 Assemblies: From Transient Interactions to Large-Scale Assembly Formation — Mehrnoosh Khodam Hazrati, Tom Miclot, and •Stepan Timr — J. Heyrovsky Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czech Republic

Human phosphofructokinase-1 (PFK1)—a key glycolytic enzyme—forms filaments and localizes into large-scale assemblies that are thought to play a major role in the regulation of glycolysis. However, the molecular interactions driving this assembly and the precise mechanisms by which it regulates the pathway remain poorly understood. In this work, we combine three levels of description—atomistic, residue-level coarse-grained, and highly coarse-grained—to characterize interactions between PFK1 tetramers and to elucidate factors governing PFK1 assembly formation. Atomistic molecular dynamics simulations of PFK1 filament interfaces reveal specific side-chain interactions that are critical for filament stability. These insights enable us to improve the description of filament formation in residue-level coarse-grained models. Using the Martini 3 and OPEPv7 coarse-grained models, we further identify key regions mediating transient PFK1–PFK1 interactions and show that these include filament-forming interfaces. Finally, we construct a highly coarse-grained model that integrates information from the more detailed simulations. Using this model, we investigate the role of membranes in PFK1 filament formation and describe how filaments may affect the recruitment of other constituents into large-scale glycolytic assemblies.

Keywords: glycolysis; enzyme assemblies; coarse-graining; molecular dynamics; protein interfaces