This page treats protein folding theory as it has been examined by science, and the implications of scientific findings for FoldIt. Although FoldIt uses heuristics and human intuition to fold proteins, these can also probably be helped along by scientific principles. Real scientists are encouraged to help the rest of us out and to correct us when we err!

The Thermodynamic HypothesisEdit

The thermodynamic hypothesis was first advanced by Nobel laureate Christian B. Anfinsen in the 1950s. Its implications for FoldIt may be summed up as follows:

  • If two different folded structures have nearly identical high scores, they are both wrong. The lowest energy state should be considerably lower than it's lowest energy form misfolded counterparts.
  • Don't let your protein become too complex. The general unrefined structure of the protein should be able to be pulled apart pretty far and find its place again -- in gaming terms, it should have considerable mojo. There should not be any knots or complexities -- a matter of protein aesthetics.

The Levinthal ParadoxEdit

The Levinthal Paradox was first noted by Cyrus Levinthal in 1969.

If the protein is to attain its correctly folded configuration by sequentially sampling all the possible conformations, it would require a time longer than the age of the universe to arrive at its correct native conformation. This is true even if conformations are sampled at rapid (nanosecond or picosecond) rates.

This paradox explains why FoldIt can exist. Proteins fold very rapidly indeed, and thus they must take a vastly shorter path to find the lowest energy state. Figuring out that path, however, is computationally hard, since it involves sampling such a gigantic array of possibilities. With proper training and study, human intuition can quickly rule out many of the obviously wrong paths and converge on the solution much faster than a computer can.

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