Refinement of low-resolution protein structures is still a major problem despite the advancements in structure prediction and refinement methods. We have recently developed a new approach, which mimics the mechanism of chaperones that rehabilitate misfolded proteins by causing them to unfold, and then giving them a new chance to refold. The target protein is unfolded by selectively pulling different ends, using geometric based simulation techniques, FRODA (1), and then refolded by the zipping and assembly method (ZAM) (2-3). During these steps, the unfolded trajectories are used to identify conserved backbone dihedral angles and hydrophobic-hydrophobic contacts, and then this acquired information is used as energetic restraints to enforce contacts and dihedral angles during refolding, through 10ns of replica-exchange molecular dynamics using the AMBER force field with implicit solvation. We have tested this refinement method on CASP9 and CASP10 targets, and observed that usually misfolded parts of the chain unfold first and most importantly refolds to produce a better refined structure.1. de Graff, Adam M.R.; Shannon, Gareth; Farrell Daniel W.; Williams, Philip M.; Thorpe, M.F. Biophys J. (2011) 101(3):736-7442. Ozkan, SB; Wu, GA; Chodera, JD; Dill, KA Proc. Natl Acad. Sci USA (2007) 104:11987-11992.3. Glembo, TJ and Ozkan SB, Biophys. J. (2011) 98:1046-1054