Make hydrophobic interactions visible

Case number:845833-992449
Topic:Game: Display
Opened by:Susume
Opened on:Saturday, April 21, 2012 - 00:47
Last modified:Friday, November 16, 2012 - 19:22

In the scientist chat on April 19 it came out that hydrophobic interactions are desirable in design puzzles, perhaps even more desirable than hydrogen bonds. The problem is, while we can see hydrogen bonds in the game, we can't see if we are making hydrophobic interactions better or worse. Would it be possible to add a coloring option to the view menu to color hydrophobic residues better or worse, based only on the portion(s) of the score that reflect hydrophobic interaction? Then we could see if we are improving the protein's ability to stick to its target. There may be some better way to implement it, but in any case, please let us see the thing you would like us to optimize.

(Sat, 04/21/2012 - 00:47  |  15 comments)

infjamc's picture
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Or better yet... why not generalize to coloring relative to a custom set of score function terms? I'm thinking about something like this:

[X] Color relative to the following score terms:
- [ ] Clashing
- [X] Packing
- [X] Hiding
- [ ] Backbone
- [ ] Side chain
- [ ] Hydrogen bonds

spmm's picture
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Well there was a recently (Oct 2011) reported discovery of an equation:

The physical model to describe the hydrophobic interactions of molecules has been a mystery that has challenged scientists and engineers since the 19th century. Hydrophobic interactions are central to explaining why oil and water don't mix, how proteins are structured, and what holds biological membranes together. Chemical engineering researchers at UC Santa Barbara have developed a novel method to study these forces at the atomic level, and have for the first time defined a mathematical equation to measure a substance's hydrophobic character.

"According to the van der Waals theory, however, oil and water shouldn't separate and surfactants shouldn't form membranes, but they do. There has been no proven theory to account for these special hydrophobic interactions. Such behaviors are crucial for life as we know it to exist."

No idea if it works :)

(PS ifjamc that -1 was me trying to page down, apologies)

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I think it would be nice to see how you are being scored on, and how it can be improved.

brow42's picture
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For custom scoring, I wrote Region Scorer: . A coloring scheme would be great! However, our colorblind cohorts are already annoyed enough.

I've been wondering how I could make use of the compatibility index in . Does this affect scoring in Rosetta? Could the effect be separated from hiding/packing?

Also, can a biochemist step in and say more about Trp-Trp bonding? I keep misreading that as Tyr-Try:

DrLemming: a short beta sheet stabilized by a cross-strand disulfide bond and two tryptophan/tryptophan interactions. The only problem: this motif is so tiny, it is difficult to do anything with; it needs to be larger but retain rigidity. Otherwise anything goes: beta sheets, alpha helix docking, rigid loops, you name it. We've given you 20 extra residues to play with.

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You'll want to look up "tryptophan stacking".

Here's a rather technical paper that discusses it:

Susume's picture
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To avoid the difficulty with colors, the hydrophobic interaction between two residues could be shown as a line connecting them (similar to a hydrogen bond but with a different texture) if its strength surpasses some threshold. The thickness of the line could indicate the degree to which the interaction increases the stickiness between the residues. The lines could be turned on and off through the view menu.

beta_helix's picture
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Thank you for bringing this up, we'll try to add a visualization to the game as soon as we can!

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As chief mouthpiece for The Colorblind Folding Contingent, I thank you in advance for considering us when making revisions to the displays of the game.

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jeff101's picture
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@spmm, I agree with your comment #2 above. It would be nice if we could change our votes on things in case we ever click the wrong button by mistake (shameless plug

tamirh's picture
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This is the visualization that should cover this now:

View Options -> Show expected residue burials

tokens's picture
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Can you say a bit more about what this viewing option actually shows? I can't really guess the logic from turning the viewing option on.

Susume's picture
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Thank you for working on this issue. I'm having trouble understanding the new visualization. It seems to highlight most of the sidechains on the outside of the protein, some in red and some in white. It is not clear to me what it means.

I was hoping for sidechains with positive "hydrophobic interactions" to be marked in some way (and sidechains lacking these interactions to remain unmarked). In a normal puzzle I expect these would be on the inside of the protein, not the outside. On a design puzzle or symmetry puzzle they might be in the space between the proteins. In the other feedback, I was hoping the buried hydrophilics on the inside of the protein could be marked to make them more visible. The added highlighting on the outside of the protein currently makes the buried ones a bit harder to find. I wonder if the new visualization can be tweaked in some way to make it concentrate on sidechains inside the protein, making the two groups I mentioned easier to see.

I also wonder if others are finding the new highlighting helpful, or have suggestions for making it more helpful.

tamirh's picture
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What it is doing right now is looking at some of the score terms of each residue and comparing the result with data from a large set of native structures. The score terms from the native structures give a range of values.

The red coloring shows where your residues are doing much worse than amino acids of the same type when compared to the native structures. The white coloring shows where your residues doing well. The intensity of the color shows you how well or how poorly the residue is doing.

Yes, the visualization can get pretty cluttered when the puzzle is large. I added both the hydrophobic and hydrophillic residues because I thought it might be useful (the score terms were not specific to hydrophobics).

I will definitely be changing the visualization, so any comments about how you think it would be better it would help.

tamirh's picture
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this is in main now


Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons