The conformation or "fold" of a protein is critical to its function in vivo or in vitro. As pharmaceutical proteins are purified by chromatography, they adsorb to surfaces and can unravel by mechanisms that are poorly understood. Our group has investigated such conformation changes by a variety of techniques, leading to detailed structural views of how proteins unfold upon adsorption to hydrophobic chromatography surfaces. In particular, complex and counterintuitive results were observed for salts, and John O'Connell and I entered into a collaboration that resulted in a four-state thermodynamic model. The approach parses the effects of salts on adsorption and unfolding and has been applied to model and pharmaceutical protein systems. In addition, we are currently investigating whether a statistical mechanical model of the protein conformational ensemble can provide parameters for the four-state model and, for the first time, predict which regions of a protein unfold upon adsorption.