Low energy pathways for reproducible in vivo protein folding

Physics – Biological Physics

Scientific paper

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Submitted to PRL on the 21st September 2010, rejected by PRL on the 20th December 2010

Scientific paper

Two proteins, one belonging to the mainly alpha class and the other belonging to the alpha/beta class, are selected to test a kinetic mechanism for protein folding. Targeted molecular dynamics is applied to generate folding pathways for those two proteins, starting from two well defined initial conformations: a fully extended and a alpha-helical conformation. The results show that for both proteins the alpha-helical initial conformation provides overall lower energy pathways to the native state. For the alpha/beta protein, 30 % (40%) of the pathways from an initial alpha-helix (fully extended) structure lead to unentangled native folds, a success rate that can be increased to 85 % by the introduction of a well-defined intermediate structure. These results open up a new direction in which to look for a solution to the protein folding problem, as detailed at the end.

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