(638a) The Structure and Stability of Alpha-Helical, Orthogonal-Bundle Proteins On Surfaces

The interaction of proteins with surfaces is a key phenomenon in many applications in medicine, biotechnology, and proteomics. Understanding protein/surface interactions is key to improving these technologies, but current understanding of the behavior of proteins on surfaces is lacking. Prevailing theories on the subject, which suggest that proteins should be stabilized when tethered to surfaces, do not explain the experimentally observed fact that proteins are often denatured on surfaces. In an attempt to develop some predictive capabilities with respect to protein/surface interactions, we previously asked the question if the stabilization/destabilization of proteins on surfaces could be correlated to secondary structure and found that no link existed. However, further investigation has revealed that proteins with similar tertiary structure show predictable stabilization patterns. In this presentation, we report how five, alpha-helical, orthogonal-bundle proteins behave on the surface compared to the bulk. By measuring stabilization using melting temperatures and the Gibbs energies of folding, we show that the stability of proteins tethered to surfaces can be correlated to the number of residues in the loop region where the tether is placed and the angle made by the alpha-helices nearest to the tether point. We also show that any destabilization that occurs because of the surface is an enthalpic effect and that surfaces always stabilize proteins entropically.