Protein Design Partition Tournament

[jeff101]

Often Design Puzzles don't let us use the
Rebuild Tool, yet other puzzles do. Will
Phase Two let us use the Rebuild Tool?

[jeff101]

Maybe pick solutions with few helix-favoring MALEK
(methionine, alanine, leucine, glutamate, or lysine)
residues. Maybe pick solutions with alternating
hydrophilic & hydrophobic residues (like sheets often
have) rather than ones with patterns that helices
often have.

[jeff101]

en.wikipedia.org

Protein secondary structure

Pages for logged out editors learn more Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common secondary structural elements are alpha helices and beta sheets, though beta turns and omega loops occur as well. Secondary structure elements typically spontaneously form as an intermediate before the protein folds into its three dimensional tertiary structure. Secondary structure is formally defined by the patte...

says proline and glycine tend to be helix-breakers
while tryptophan, tyrosine, phenylalanine, isoleucine,
valine, and threonine prefer to adopt β-strand conformations.

[bkoep]

The Rebuild tool will be enabled in the Phase Two contests; however, it has been disabled in the Phase One design puzzle.

[Susume]

A player could challenge their own design in Phase 1, to try to figure out how easy it is to challenge, before they pick one to submit. Can you easily rearrange part of it and get a similar score? If you can, others can as well.

[Susume]

Is improving the partition function the same as negative design?

[bkoep]

In protein engineering, "negative design" is any kind of design that is meant to destabilize a particular state (to increase the absolute energy of that state), rather than stabilize that state (decrease its energy). Usually this is used to bias the partition function towards another desired state. In our tournament, for example, you could try to bias the partition function toward your design by anticipating potential decoys, and changing your design sequence to decrease the score (increase the energy) of those decoys. In this case you would carry out "negative design" of the decoy states.

Negative design can also be useful for improving the specificity of protein interactions. If you design your protein to bind some target, but you discover that your protein also binds to other targets (and causes unwanted side effects, maybe), you could use negative design to eliminate off-target binding. For example, see Figures 2 and 6 of this paper.

On the other hand, there are applications where you might want to reduce the bias in a protein's partition function, so that your protein can exchange between two states easily. Suppose you want your protein to act like a switch, so that it changes state in response to subtle changes in the environment—or maybe you just want to study how a protein exchanges between two folds. See this paper for an extreme example of this kind of negative design.

[jeff101]

Will you list which players' designs from Phase One are chosen for Phase Two? Will each Phase Two contest title include the name of the player who designed the contest's starting structure?

Thanks again,
Jeff

[bkoep]

The title of each Phase Two contest will include the username of the player who designed the target.

[jeff101]

Do you know when Phase Two will begin? Will you make a big announcement when it starts? Will Phase Two be a bunch of Science Puzzles or will it be a bunch of Contests?