Importance of Protein Context on the Unfolding Pathways of β-hairpins

Abstract

Small β-hairpin peptides as well as three-stranded WW domains have been used as models for the folding of β-hairpins in larger proteins. Previous studies of the FBP28 WW domain proposed that side chain contacts between residues in the strands and not the precise order of backbone hydrogen bond formation guide β-hairpin folding. But how applicable is the folding of model systems, such as FBP28 WW domain, to the folding of β-structure in larger proteins with conventional hydrophobic cores? Here we present multiple unfolding molecular dynamics simulations of three proteins that share a double hairpin motif structurally similar to WW domains: cold shock protein A (CspA), cold shock protein B (CspB) and glucose permease IIA domain.