Structural comparison of the two alternative transition states for folding of TI I27.

ABSTRACT: TI I27, a beta-sandwich domain from the human muscle protein titin, has been shown to fold via two alternative pathways, which correspond to a change in the folding mechanism. Under physiological conditions, TI I27 folds by a classical nucleation-condensation mechanism (diffuse transition state), whereas at extreme conditions of temperature and denaturant it switches to having a polarized transition state. We have used experimental Phi-values as restraints in ensemble-averaged molecular dynamics simulations to determine the ensembles of structures representing the two transition states. The comparison of these ensembles indicates that when native interactions are substantially weakened, a protein may still be able to fold if it can access an alternative transition state characterized by a

SUBMITTER: Geierhaas CD 

PROVIDER: S-EPMC1479071 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature