Hydrogen exchange experiments reveal the existence of a foldon structure in Cytochrome c. We performed constant temperature Molecular Dynamics simulations of Cytochrome c to investigate the macroscopic behavior of the foldons. The results showed that the tertiary interactions in Cytochrome c play an important role in the stabilization of the N- and C-terminal helices. We also observed the macroscopic behavior of a black foldon in the process of thermal unfolding. Our results support that Cytochrome c folding occurs in accordance with the classical pathway concept of Levinthal. (c) 2009 Elsevier B.V. All rights reserved.