Berlin 2005 – wissenschaftliches Programm

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AKB: Biologische Physik

AKB 90: Protein Folding and Molecular Dynamics

AKB 90.3: Vortrag

Mittwoch, 9. März 2005, 14:30–14:45, TU H2013

Molecular mechanism of urea-induced protein unfolding — •Martin Stumpe and Helmut Grubmüller — MPI für biophysikalische Chemie, Theoretische und computergestützte Biophysik, Am Fassberg 11, 37077 Göttingen

Chemical denaturation is widely used to analyse protein stability and unfolding. Despite the common use of urea as denaturant, little is known about the molecular mechanism of urea-induced protein unfolding. Both, a direct interaction between urea and the protein as well as an indirect interaction via alteration of the water structure are possible and have been discussed. To shed light on this mechnism, we have carried out molecular dynamics simulations. Our studies of urea-water solutions revealed only minor perturbations of the water structure by the presence of urea. This finding provides new support for the direct interaction of urea with proteins during unfolding. We also achieved a detailled understanding of urea self-aggregation. Unfolding-simulations were performed with the Cold-Shock protein Bc-Csp and the human Prion protein fragment at elevated temperatures in physiological environment and in 8M urea solution. For these proteins, temperature-induced unfolding starts with a loss of secondary structure while the tertiary structure is conserved at the beginning and starts to decay only after the proteins have lost a substantial amount of secondary structure, in line with the hydrophobic-collapse models. Unexpectedly, and in contrast to room temperature results, at high temperatures urea does not seem to accelerate unfolding, which might point towards an entropy-dominated unfolding mechnism.