Berlin 2018 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 12: Computational Biophysics I
BP 12.10: Vortrag
Dienstag, 13. März 2018, 12:15–12:30, H 1058
Metadynamics Simulations of the Fibrinogen Protomer — •Timo Schäfer1,2, Lorenz Ripka1, Friederike Schmid1, and Giovanni Settanni1,3 — 1Johannes Gutenberg-University Mainz — 2Graduate School Materials Science in Mainz — 3Max Planck Graduate Center with the Johannes Gutenberg-University Mainz
Fibrinogen is a dimeric multi-chain serum protein that polymerizes into fibrin when activated by thrombin as part of the coagulation cascade. Fibrinolysis, the cleavage of fibrin by the enzyme plasmin, controls the dissolution of blood clots. While the major factors contributing to fibrin formation and dissolution have been identified, the atomistic details of these mechanisms are largely unknown.
Here, the connection between structure and function of fibrinogen is studied using classical atomistic molecular dynamics simulations coupled to metadynamics, a technique that allows for a thorough exploration of the important degrees of freedom of the system. Based on our previous characterization of a hinge along the coiled-coil region of the fibrinogen protomer, we used metadynamics to explore the major degrees of freedom related to this hinge, represented by the two largest principal components of motion. The simulations reveal the presence of two specifically distinct modes of bending, characterized by a different loss of secondary structure and exposure of plasmin cleavage sites. The bending modes occur in plane to the available models of double-stranded fibrin protofibrils. We show how they could be integrated into available models of fibrin protofibril formation and play a role in fibrinolysis