Context is a major determinant of beta-sheet propensity.

Residues in beta-sheets occur in two distinct tertiary contexts: central strands, bordered on both sides by other beta-strands, and edge strands, bordered on only a single side by another beta-strand. The delta delta G values for beta-sheet formation measured at an edge beta-strand of the IgG-binding domain of protein G(GB1) are quite different from those obtained previously at a central position in the same protein. In particular, there is no correlation at the edge position with statistically determined beta-sheet-forming preferences. The differences between beta-sheet propensities measured at central and edge beta-strands, delta delta delta G values, correlate with the values of water/octanol transfer free energies and side-chain non-polar surface area for the amino acids. These results strongly suggest that, unlike alpha-helix formation, beta-sheet formation is determined in large part by tertiary context, even at solvent-accessible sites, and not by intrinsic secondary structure preferences.