Molecular Dynamics Simulations of Unfolding and Refolding of a β -Hairpin Fragment of Protein G

We have studied the unfolding and refolding pathway of a β -hairpin fragment of protein G by using molecular dynamics. Although this fragment is small, it possesses several of the qualities ascribed to small proteins: cooperatively formed β -sheet secondary structure and a hydrophobic "core" of packed side chains. At high temperatures, we find that the β -hairpin unfolds through a series of sudden, discrete conformational changes. These changes occur between states that are identified with the folded state, a pair of partially unfolded kinetic intermediates, and the unfolded state. To study refolding at low temperatures, we perform a series of short simulations starting from the transition states of the discrete transitions determined by the unfolding simulations.