The application of the recently developed integrated tempering sampling (ITS) method to protein folding simulations allowed us to quantitatively determine the folding free energy landscape of a number of polypeptides. It was found that the folding free energy landscapes of simple beta-hairpins, thus also their folding mechanisms, are sensitive to the amino acid sequence. Both turn stability and hydrophobicity of polypeptides affect strongly their hydrogen bond assembly. We then briefly discuss the molecular mechanisms through which alcohols and inorganic salts affect polypeptide structure formation and hydration. For example, the addition of NaI to the aqueous solution of BBA5 caused its denaturation and significantly weakened hydrogen bonds of the polypeptide. Na2SO3, a �kosmotropes,� strengthened the hydrophobic interactions and increased hydrogen bonding of the polypeptide. Finally, we will discuss the molecular mechanism through which monohydric methanol and TFE denature BBA5, and polyhydric glycol and glycerol protect the polypeptide structure.

Folding simulation of polypeptides, free energy landscape calculation and effects of solvation

243rd National Meeting (2012)

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