Folding and unfolding of the three-stranded beta-sheet peptide Beta3s

The conformational space of Beta3s, a 20-residue three-stranded antiparallel β-sheet peptide (double hairpin), is sampled close to the melting temperature (330 K) by implicit solvent (SASA) molecular dynamics simulations for a total of 20 μs (Muff S. and Caflisch A., Proteins: Struct. Funct. & Bioinf., 70, 1185-1195, 2008). Strikingly, the denatured state ensemble of Beta3s is very heterogeneous and includes conformations with partial helical structure and fluctuating unstructured residues as well as mainly enthalpic traps with one of the two native hairpins formed (Rao F. and Caflisch A., J. Mol. Biol. 342, 299-306, 2004). Here, one of the about 100 unfolding and refolding events are shown (150 ns), during which partially helical conformations are visited in the denatured state. Folding starts with formation of the C-terminal hairpin followed by association of the N-terminal strand. This sequence of events is one of the two main folding pathways. The N-terminus is in blue while residues Gly6-Ser7 and Gly14-Ser15 (which form tight turns in the native state) are colored in yellow.