Pathways for folding and re-unfolding transitions in denatured conformations of anhydrous proteins

Using molecular dynamics simulations, we explore the mechanism that may underlie the type of folding transitions observed experimentally in anhydrous proteins. Recent relaxation studies of a partly unfolded alpha-helical bundle suggest an approach to simulating cycles of folding/re-unfolding transitions. Here, we provide evidence that such processes may be general, by uncovering a similar relaxation pattern in lysozyme, a more flexible alpha/beta protein. We find that, while refolding is initiated by partial polymer collapse, the reversible re-unfolding of compact normative structures proceeds as a correlated transition not unlike the direct unfolding of lysozyme from its native state. (C) 2003 Elsevier Science B.V. All rights reserved.