The Trp Cage: Folding Kinetics and Unfolded State Topology via Molecular Dynamics Simulations

Abstract
Using over 75 μs of molecular dynamics simulation, we have generated several thousand folding simulations of the 20-residue Trp cage at experimental temperature and solvent viscosity. A total of 116 independent folding simulations reach RMSDcα values below 3 Å RMSDcα, some as close as 1.4 Å RMSDcα. We estimate a folding time of 5.5±3.5 μs, a rate that is in reasonable agreement with experimental kinetics. Finally, we characterize both the folded and unfolded ensemble under native conditions and note that the average topology of the unfolded ensemble is very similar to the topology of the native state.

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