Study of the stability and unfolding mechanism of BBA1 by molecular dynamics simulations at different temperatures

BBA1 is a designed protein that has only 23 residues. It is the smallest pr otein without disulfide bridges that has a well-defined tertiary structure in solution. We have performed unfolding molecular dynamics simulations on BBA1 and some of its mutants at 300, 330, 360, and 300 K to study their kin etic stability as well as the unfolding mechanism of BBA1. It was shown tha t the unfolding simulations can provide insights into the forces that stabi lize the protein. Packing, hydrophobic interactions, and a salt bridge betw een Asp12 and Lys16 were found to be important to the protein's stability. The unfolding of BBA1 goes through two major steps: (1) disruption of the h ydrophobic core and (2) unfolding of the helix. The beta-hairpin remains st able in the unfolding because of the high stability of the type II' turn co nnecting the two beta-strands.