puzzle picture
1054: Vancomycin Binder: Shape Complementarity
Status: Closed

Summary

Name: 1054: Vancomycin Binder: Shape Complementarity
Status: Closed
Created: 02/12/2015
Points: 100
Expired: 02/27/2015 - 06:00
Difficulty: Intermediate
Description: Design a binding pocket for vancomycin! Antibiotic resistance is an increasing problem and one of the last resorts for treating inflammation is the cyclic peptide vancomycin. Hence there is a general interest to generate proteins that can bind vancomycin and upon binding generate a signal. With this technology it would be possible to test patients that have been treated with antibiotics if they still have small amounts left before they leave e.g. a hospital. The aim of this puzzle is to optimize the interaction between a protein and the small molecule vancomycin.

This puzzle also introduces the new Shape Complementarity filter. Shape complementarity is a measure of how well the ligand's surface contours match the cavity of the binding pocket, and has been shown to be a good discriminator between binders and non-binders. Use the "Show Isosurface" view option to visualize the protein surface, and increase shape complementarity to improve your score!
Categories: Design, Overall

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Comments

spmm's picture
User offline. Last seen 45 weeks 2 days ago. Offline
Joined: 08/05/2010
Groups: Void Crushers
please miss!

mine's broken - Mac Yosemite - the black cloud goes if I turn the isosurface off and it didn't crash, moving the ligand about doesn't fix it.

http://fold.it/portal/files/chatimg/irc_179219_1424425184.png

bkoep's picture
User offline. Last seen 18 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: None
We'll take a look

Thanks for all the bug reports relating to the "Show Isosurface" option! We'll try to reproduce these on our end and see if we can figure out the problem.

Joined: 08/30/2011
I'm sure you are also

I'm sure you are also interested in different orientations of the vancomycin and the corresponding folds?

bkoep's picture
User offline. Last seen 18 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: None
Yes!

Clearly, we'd like players to focus on building a binding pocket on the concave side of the protein (where mutations are allowed).

But, by all means, experiment with different orientations of the ligand in the binding pocket to maximize packing and shape complementarity!

stomjoh's picture
User offline. Last seen 10 weeks 2 days ago. Offline
Joined: 11/18/2012
Groups: None
Somehow the filter doesn't seem to be working quite right...

I know the comment says to look at other orientations, but if the ligand is completely outside of the pocket adjacent to the perimeter/arc of the protein I wouldn't expect to see a Complementarity score of +1459.2. Is that really right?!?

http://fold.it/portal/files/chatimg/irc_465750_1424726172.png

Joined: 11/03/2011
shape complementarity

What is the maximum amount permissible for shape complementarity ?

bkoep's picture
User offline. Last seen 18 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: None
Maximum 1500 points

In this puzzle, players can receive a maximum of 1500 points from the Shape Complementarity filter. But beware, there is a steep penalty if your shape complementarity drops too low, and the bonus will jump from 1250 to 250!

Joined: 09/24/2012
Groups: Go Science
in the cloud

(Windows 7) The cloud appears or not when cliking on "Show Isosurface" depending on the solution I load. Even then , it sometimes arrounds also the ligan or not.
And I do not see any change when clicking on "show" for the new filter.

Joined: 09/24/2012
Groups: Go Science
here a picture

Joined: 09/24/2012
Groups: Go Science
and another strange display

Here I see the cloud, but see on the left the strange black ligand

Joined: 08/09/2010
rebuild?

locked segments can be rebuilded, a bug?

Joined: 08/09/2010
cut

and cut works too :-?

Joined: 06/06/2013
Groups: Gargleblasters
tools needed

I have not found the cloud. That might be good. I would like a tool that lets me see sidechain links between the ligand and main protein only, not all sidechain links. If we have a lot of these puzzles, it would be very helpful. this is running slowly and the display is very jerky due to the large puzzle size.... simpler info of the right kind would be useful

spmm's picture
User offline. Last seen 45 weeks 2 days ago. Offline
Joined: 08/05/2010
Groups: Void Crushers
View isosurface

Is turned on and off in the view menu, it is more of a translucent skin covering the bones to show the surface than an unattached cloud. We cant see hydrophobic bonds anywhere - not just about hydrogen bonds

jamiexq's picture
User offline. Last seen 11 hours 56 min ago. Offline
Joined: 07/31/2011
purpose to rebuild pocket

If the purpose is to focus on and change (rebuild) the pocket - then why can't we idealize those segments?

pauldunn's picture
User offline. Last seen 5 days 18 hours ago. Offline
Joined: 09/20/2010
Groups: Go Science
subscore name

I can't find "Shape Complementarity" in the return value for puzzle.GetPuzzleSubscoreNames. Is this intentional?

viosca's picture
User offline. Last seen 1 year 23 weeks ago. Offline
Joined: 10/16/2013
I noticed that it does appear in the notes.

I noticed that it does appear in the notes.

Joined: 10/30/2012
Groups: Beta Folders
not sure if this is going to

not sure if this is going to work, team pattern is consistent, highest scores are outside the pocket,

after getting a good position with some side-chain interaction, shake side-chains and wiggle causes it to move away from the pocket,

tried running an idealized script, mutate no wiggle, c&ws early in order to stabilize the protean. it was better and will share to scientists if you like, but would not stay in contact.

Joined: 06/06/2013
Groups: Gargleblasters
agree with michael -- please post reply here after puzzle closes

I got good bonds down one side of protein (5, with both ends and 3 in middle). banded them. will share, but best score is to abandon the bonds. I have a smaller machine and team. I'm sure some bonds in the middle of the other side too might have helped. but this puzzle doesn't work as intended. any more like it seems like a waste of our time. perhaps scientists can post here after the close.
obviously 5 bonds spread out are not enough to hold over the clashing penalty. what is? need to rethink this.

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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, RosettaCommons