Molecular dynamics simulations of unfolding and refolding of a beta-hairpin fragment of protein G

We have studied the unfolding and refolding pathway of a beta-hairpin fragm ent of protein G by using molecular dynamics. Although this fragment is sma ll, it possesses several of the qualities ascribed to small proteins: coope ratively formed beta-sheet secondary structure and a hydrophobic "core'' of packed side chains. At high temperatures, we find that the beta-hairpin un folds through a series of sudden, discrete conformational changes. These ch anges occur between states that are identified with the folded state, a pai r of partially unfolded kinetic intermediates, and the unfolded state. To s tudy refolding at low temperatures, we perform a series of short simulation s starting from the transition states of the discrete transitions determine d by the unfolding simulations.