Wood, Geoffrey P. F.Rothlisberger, Ursula2011-05-022011-05-022011-05-02201110.1021/ct200156ehttps://infoscience.epfl.ch/handle/20.500.14299/66935WOS:000290293000032The distinct conformational dependence of chemical shifts caused by R-helices and β-sheets renders NMR chemical shift analysis a powerful tool for the structural determination of proteins. However, the time scale of NMR experiments can make a secondary structure assignment of highly flexible peptides or proteins, which may be converting between conformational substates, problematic. For instance the amyloid-β monomer, according to NMR chemical shifts, adopts a predominately random coil struc- ture in aqueous solution (with <3% R-helical content). Molecular dynamics simulations, on the other hand, suggest that R-helical content can be significant (10␣25%). In this paper, we explore the possible reasons for this discrepancy and show that the different results from experiments and theory are not necessarily mutually exclusive but may reflect a general problem of secondary structure assignment of conformationally flexible biomolecules.Replica-Exchange SimulationsMolecular-Dynamics SimulationsAlzheimers-DiseaseProtein FibrillogenesisStructure ReservoirForce-FieldAmino-AcidsNmrTemperatureModeltext::journal::journal article::research article