Molecular Dynamics Simulations of the Folding Kinetics
of Cytochrome C: The Role of Non-Native Contacts

ALFREDO E. C´ARDENAS AND RON ELBER
Department of Computer Science
Cornell University
Ithaca, NY 14853, USA
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Abstract:

The folding kinetics of the 104-amino acid cytochrome c is studied using the Stochastic Difference Equation (SDE) algorithm. This algorithm solves the classical action approximately using a long length step. Twenty-six folding trajectories at room temperature are obtained using a full atomic description for the protein and an implicit solvent model for water. The simulations are in agreement with experimental observations: the early collapse during the folding without significant formation of secondary structure, and the earlier formation of the N- and C-helices compared to the 60Ís-helix. The dynamics of the formation of non-native contacts is examined as well. It is observed that there is a large fraction of non-native contacts at the unfolded compact (or molten globule) configuration of cytochrome c. A detailed analysis of the simulations shows that the molten globule is flexible enough to allow the elimination of these wrong contacts before reaching the folded native structure.