Characterization of folding mechanisms of Trp-cage and WW-domain by network analysis of simulations with a hybrid-resolution model.

ABSTRACT: In this study, we apply a hybrid-resolution model, namely, PACE, to characterize the free energy surfaces (FESs) of Trp-cage and a WW-domain variant along with the respective folding mechanisms. Unbiased, independent simulations with PACE are found to achieve together multiple folding and unfolding events for both proteins, allowing us to perform network analysis of the FESs to identify folding pathways. PACE reproduces for both proteins expected complexity hidden in the folding FESs, in particular metastable non-native intermediates. Pathway analysis shows that some of these intermediates are, actually, on-pathway folding intermediates and that intermediates kinetically closest to the native states can be either critical on-pathway or off-pathway intermediates, depending on the protein. A

SUBMITTER: Han W 

PROVIDER: S-EPMC3811923 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature