Modeling Unfolded States of Proteins and Peptides. II. Backbone Solvent Accessibility

Abstract

Buried surface area is often used as a measure of the contribution to protein folding from the hydrophobic effect. Quantitatively, the surface buried upon folding is reckoned as the difference in area between the native and unfolded states. This calculation is well defined for a known structure but model-dependent for the unfolded state. In a previous paper [Creamer, T. P., Srinivasan, R., & Rose, G. D. (1995) Biochemistry34, 16245−16250], we developed two models that bracket the surface area of the unfolded state between limiting extremes. Using these extrema, it was shown that earlier models, such as an extended tripeptide, overestimate the surface area of side chains in the unfolded state. In this sequel to our previous paper, we focus on backbone surface in the unfolded state, again adopting the strategy of trapping the area between limiting extrema. A principal conclusion of this present study is that most backbone surface in proteins is buried within local structure.