School of thought in the
protein folding community that differs from the classical model of
protein folding. The classical model states that folding of a protein occurs through specific intermediates. In other words, a protein folds through a pathway:
unfolded -> intermediate1 -> intermediate2 -> folded
The folding funnel hypothesis states that there is no one specific pathway that a protein folds along. Instead, a protein runs down a multi-dimensional funnel towards the final structure. There are a large number of possible intermediates between the fully unfolded and fully folded protein. There is no physical funnel, of course. Its just another way of conceptualizing a complex reaction coordinate.
schematic of a folding funnel
(------- entropy -------)
^ \ / - fully unfolded protein
| \ /
| -\ /
| | -
| \ /
| energy \ /
| \ | many partially folded
| | / intermediates
| \ /
| --\ |
| | /
v \ /
\ /
\ /
X - folded protein
The ruggedness of the funnel surface can represent the presence of
kinetic traps to folding, where the protein gets stuck in
misfolded intermediates. One can think of a folding protein as a person
skiing down a slope. If the slope is smooth and steep, the person is going to reach the bottom quickly. If the slope is shallow, or has a lot of bumps and pits, or both, then it will take longer to get to the bottom.