Determining the mechanism by which proteins attain their native structure is an important but difficult problem in basic biology. The study of protein folding is difficult because it involves the identification and characterization of folding intermediates that are only very transiently present. Disulfide bond formation is thermodynamically linked to protein folding. The availability of thiol t...

Bovine α-lactalbumin (αLA) has four disulfide (SS) bonds in the native form (N). On the oxidative folding pathways of this protein, two specific SS folding intermediates, i.e., (61-77, 73-91) and des[6-120], which have two and three native SS bonds, respectively, accumulate predominantly in the presence of Ca2+. In this study, we reinvestigated the pathways using a water-soluble cyclic selenoxi...

In this work we studied the folding process of the hybrid-1 type human telomeric DNA G-quadruplex with solvent and K(+) ions explicitly modeled. Enabled by the powerful bias-exchange metadynamics and large-scale conventional molecular dynamic simulations, the free energy landscape of this G-DNA was obtained for the first time and four folding intermediates were identified, including a triplex a...

Most bacterial exported proteins cross the cytoplasmic membrane as unfolded polypeptides. However, little is known about how they fold during or after this process due to the difficulty in detecting folding intermediates. Here we identify cotranslational and posttranslational folding intermediates of a periplasmic protein in which the protein and DsbA, a periplasmic disulfide bond-forming enzym...