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

Christopher D. Snow, Bojan Zagrovic, and Vijay S. Pande. Journal of the Americal Chemical Society (2002)

ABSTRACT: A number of rapidly folding proteins have been characterized in recent years.1 These small proteins can provide the first direct comparisons between simulated and experimental protein folding kinetics and pathways. Proteins have been characterized through thermodynamic sampling methods, unfolding simulations, and folding simulations using simple potentials. Here, as described recently, we use several thousand stochastic dynamics simulations in a generalized-Born implicit solvent (in atomic detail) to simulate the folding dynamics of the Trp cage mini-protein under experimental conditions (27 °C with full solvent viscosity,) 91 ps-1). The Folding@home distributed computing project was used to generate an aggregate simulation time of ~100 us (~250 CPU years). First we capture the rapid relaxation from an extended starting condition to a relaxed unfolded state ensemble of thousands of conformations. With continued simulation, a small fraction of these simulations reach the folded state. Furthermore, the topology of the collapsed unfolded state closely resembles the native state.