| Abstract
| - Folding pathways of the B domain of staphylococcal protein A have been sampled with a distributed computingapproach. Starting from an extended structure, the method employs an index measuring topological similarityto the native structure to selectively sample trajectory branches leading to the native fold. Unperturbed andcontinuous folding trajectories are drawn on a physics-based atomic potential energy surface with an implicitsolvent. The sampled folding trajectories demonstrate a similar sequence of events: the earlier stage involvesa partial formation of helix 2 and to a less extent of helix 1 at their N terminals, followed by the hydrophobiccollapse between residues F14, I17, and L18 on helix 1 and residues R28, F31, and I32 on helix 2, whichresults in the rigidification of the helix turn from R28 to I32. Helix 2 is then able to extend, allowing for theformation to turn 2. The above description explains one experimental result why a G30A mutant of the proteinwas observed to be the fastest folder among proteins of its size. And the ensemble of structures right beforethe final collapse is in good agreement with the transition state ensemble mapped by another recent experimentwith Fersht Φ values. We emphasize that because the approach here does not provide quantifications of thefree energy landscape, our model of the transition state ensemble emerges from comparisons of simulationsand previous experimental results rather from the simulation results alone. On the other hand, as our approachdoes not rely on a low-dimensional free energy surface, it can complement methods based on the constructionof free energy surfaces.
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