Probing the non-covalent forces key to the thermodynamics of β-hairpin unfolding.

Although it is well understood that the graph of the free energy of unfolding (Δ) of a globular protein with temperature approximates to a negative parabola, there is as yet no link between this global (G) Δ () function and the individual structural elements-residue type and the non-covalent forces between groups-contributing to it. As such, there is little understanding of how each structural element contributes to the globally assessed changes of enthalpy (Δ ), entropy (Δ ), and heat capacity (Δ ) of unfolding calculated from the Δ () function. To address this situation, we consider here an alternative approach to examining fold stability.

Assessing Weak Anion Binding to Small Peptides.

Since Hofmeister's seminal studies in the late 19th century, it has been known that salts and buffers can drastically affect the properties of peptides and proteins. These Hofmeister effects can be conceived of in terms of three distinct phenomena/mechanisms: water-salt interactions that indirectly induce the salting-out of a protein by water sequestration by the salt, and direct salt-protein interactions that can either salt-in or salt-out the protein. Unfortunately, direct salt-protein interactions responsible for Hofmeister effects are weak and difficult to quantify.