Molecular dynamics simulations from putative transition states of alpha-spectrin SH3 domain

A series of molecular dynamics simulations in explicit solvent were started from nine structural models of the transition state of the SH3 domain of alpha-spectrin, which were generated by Lindorff-Larsen et al. (Nat Struct Mol Biol 2004;11:443-449) using molecular dynamics simulations in which experimental Phi - values were incorporated as restraints. Two of the nine models were simulated 10 times for 200 ns and the remaining models simulated two times for 200 ns. Complete folding was observed in one case, while in the other simulations partial folding or unfolding events were observed, which were characterized by a regularization of elements of secondary structure. These results are consistent with recent experimental evidence that the folding of SH3 domains involves low populated intermediate states.