Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Phase transition from α-helices to β-sheets in fibrinogen coiled coils
Mechanical functions of fibrin fibers are essential for hemostasis and wound healing (1). Fibrinogen, the precursor of fibrin, is a branched polymer that provides the scaffold for a thrombus in vertebrates. The physical properties of fibrin(ogen) are essential for the ability of fibrin clots to accomplish hemostasis and are an important determinant of the pathological properties of thrombi. Despite such critical importance, the structural basis of fibrin clot mechanics is not well understood (2). Graphics Processing Units (GPUs) are being used in a variety of scientific applications, including the biological N-body problem (3). We carried out theoretical studies of the mechanical properties of fibrinogen molecule, using all-atom Molecular Dynamics (MD) simulations in implicit water fully implemented on a GPU. When the α-helical regions in the coiled-coils are subject to an external mechanical perturbation, they undergo reversible phase transition to form the extended β-sheets (4). The D-regions of the molecule make several turns around the direction of force application to accommodate the mechanical unraveling of the coiled coils. As a result, the hydrophobic side-chains buried inside the α-helices in the fibrin(ogen) folded state become exposed to solvent. We argue that the observed increase in the free energy of solvation might lead to protein aggregation, and hypothesize that these transitions provide the molecular mechanism for the negative compressibility observed in experiments on whole blood clots (5). These results provide important quantitative characteristics of the fibrinogen nanomechanics necessary to understand the viscoelastic properties of fibrin polymers at the fiber and whole clot levels.
This work has been supported by the American Heart Association grant (09SDG2460023) and by the Russian Ministry of Education grant (02−740−11−5126).
1Department of Chemistry, University of Massachusetts, Lowell, MA 01854