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1150: 60 Residue Symmetric Dimer Design: Limited HBonds
Status: Closed

Summary

Name: 1150: 60 Residue Symmetric Dimer Design: Limited HBonds
Status: Closed
Created: 10/19/2015
Points: 100
Expired: 10/26/2015 - 23:00
Difficulty: Intermediate
Description: In this puzzle, the bonus for Hbond networks has been increased, but only Hbond networks that are at least 75% satisfied will be rewarded. Furthermore, no more than three inter-molecular Hbonds may contribute to the filter! There are several other filters in effect; see the puzzle comments for details. The Baker Lab will run folding predictions on your solutions for this puzzle, and those that perform well will be synthesized in the lab. Remember, you can use the Upload for Scientists button for up to 5 designs that you want us to look at, even if they are not the best-scoring solutions!
Categories: Design, Overall, Symmetry

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Comments

bkoep's picture
User offline. Last seen 13 hours 1 min ago. Offline
Joined: 11/15/2012
Groups: None
Filters

Residue IE Score: Monitors that all PHE, TYR, and TRP residues are scoring well.

HBond Network: Rewards networks comprising at least three hydrogen bonds, with 1-3 hydrogen bonds spanning the dimer interface. In addition, at least 75% of all polar atoms in the network must make hydrogen bonds.

Core Existence: Monomer: Ensures that at least 18 residues are buried in the core of the monomer unit.

Core Existence: Complex: Ensures that at least 48 residues are buried in the core of the entire complex (including the interface between monomer units).

Fragment Score: Scans for parts of your design that are unlikely to fold up naturally. Use Rebuild and Remix tools to fix these regions of your design!

Joined: 04/10/2015
Groups: Beta Folders
Question

Can you make a trimmer puzzle or double dimmer with Hbonds?

Just curious, why the constraint for 1-3 hydrogen bonds spanning the dimer interface?

bkoep's picture
User offline. Last seen 13 hours 1 min ago. Offline
Joined: 11/15/2012
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Absolutely!

We're looking forward to trying out the HBNet Filter with more complex symmetries, but we want to nail down the basics first.

The reason for the new constraint is that some players were able to attain high filter scores with a single, massive network at the interface. This is actually bad for binding, and we wanted to discourage that! Instead, we like to see small, completely satisfied HBond networks at an interface that is mostly nonpolar.

Joined: 04/10/2015
Groups: Beta Folders
Thanks for the answer

Thank you very much for the answer.

I understand your point regarding binding and nonpolar interface...

Is it posible to distiguish from the outside interface bonds and the inner interface? Ideally the hbonds should be on the outside interface... moreover If we can find an Hbond network like a "sewing machine" or somekind of leapfrog pattern...

Could it be posible to have the filter taking in consideration the monomer bonds instead the interface bonds?

bkoep's picture
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Joined: 11/15/2012
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To clarify

Actually, interface H-bonds will ideally be buried at the interface. The problem is that massive, nonpolar interfaces are nonspecific—they will bind to any other decoys with a nonpolar surface.

Ideal interface H-bonds confer specificity because they are extremely difficult to satisfy. Decoy binding partners will not satisfy all the interface H-bonds and will not bind; only the designed target will satisfy these H-bonds when it binds the interface.

If you place your H-bond network on the "outer interface," it can probably be satisfied with surrounding water, regardless of the binding partner. This is not ideal, because other nonpolar decoys can still bind just as well as the target.

Joined: 04/10/2015
Groups: Beta Folders
Thanks again for the clarification

More clear every time...specially with:

"...Actually, interface H-bonds will ideally be buried at the interface..."
and "...If you place your H-bond network on the "outer interface," it can probably be satisfied with surrounding water, regardless of the binding partner..."

Most of the high scoring pieces do have the H-bonds on the "outer interface", if I have to guess, I said it is because you do have more room to maneuver the polar AAs in order to make the h-bonds...

Will it be possible to assign more filter bonus to "inner interfase" H-bonds like for example serine or threonine? Or even better not considering the H-bond network on the "outer interface".

Susume's picture
User offline. Last seen 3 hours 41 min ago. Offline
Joined: 10/02/2011
Meaning of "no more than three"

Does "no more than three inter-molecular Hbonds" mean that if there are more than 3, only 3 will be given points, or if there are more than 3 the whole network will not count? And if the limit of 3 is inter-molecular, does that mean there can be additional bonds in that network as long as they are on the monomer?

bkoep's picture
User offline. Last seen 13 hours 1 min ago. Offline
Joined: 11/15/2012
Groups: None
Only three bonds are scored

A network with more than three inter-molecular Hbonds is still valid. However, no more than three of those inter-molecular Hbonds will contribute to the filter score.

Likewise, the number of additional bonds in the monomer will not affect the filter score. The satisfaction of those residues will affect the filter score.

I apologize that this filter scheme may seem nonintuitive. As a final reminder, recall from the HBNet blogpost that the score for a network depends only on the number of intermolecular Hbonds and the satisfaction of the entire network.

Joined: 04/10/2015
Groups: Beta Folders
Thanks

Thank for the clarification on the filter score... do you know why that three limit?

Could be posible to have a puzzle with filter bonus with the number of Hbonds instead of intermolecular Hbonds?

Joined: 10/30/2012
Groups: Beta Folders
good question

good question

Joined: 04/10/2015
Groups: Beta Folders
Very good question...

Very good question... however it will be an amazing challenge for me to understand the question/answer in english... ;)

Maybe you can clarify in several languages... like english, spanish, etc... :)

Susume's picture
User offline. Last seen 3 hours 41 min ago. Offline
Joined: 10/02/2011
Unhelpful messages

I have received the following confusing messages when hovering over blue bond networks: "Interface HBonds: 0 (2 over limit)" and "Interface HBonds: 0 (3 over limit)". How can 0 be over the limit? Shared the second one with scientists as "Confusing Message 2". As far as I could tell there were 3 blue interface bonds and 1 blue monomer bond at the time, although it's hard to tell because one was a sidechain-to-backbone bond and the graphics for those terminate in empty space so it's hard to tell what they connect to. None of the bonds were scoring because satisfaction was too low.

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