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1855: Y1 Receptor ligand design

Closed since over 2 years ago

Intermediate Small Molecule Design

Summary


Created
June 17, 2020
Expires
Max points
100
Description

Use the new reaction design tool (blog post) to build a ligand which will bind well to the Y1 Receptor.



We've started you off with an arginine sidechain known to bind in the Y1 pocket. You can use the reaction design tool to grow this molecule to better fill the pocket. The molecules we're interested in at the moment are based on a central arginine core with "decorations" on either side. The reaction design tool will allow you to pick the best combination.



Since the precise 3D structure of the ligand is important, some of the reagent choices are very similar, except for the details of how the atoms are arranged (specifically, their chirality).



For more information about the Y1 receptor, see the previous puzzles: 1441, 1446, 1503 and 1653

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Comments


Xartos Lv 1

Cant open the new puzzle the client always crashes when i try to open it. Even after redownloading the puzzle still the same.

LociOiling Lv 1

I accidentally downvoted Xartos' post, and can't fix it.

I'm also getting an instant crash on 1855 using 20200618-bbc43b61c3-win_x86-devprev.

rmoretti Staff Lv 1

Thanks for the report. We're looking into it.

It seems to be inconsistent, so retrying a few times may help. Some other things that have been reported as a workaround are to try loading the puzzle from within another puzzle (versus from the main screen), or tweaking your view options in another puzzle prior to loading 1855. Also, some people have had success with deleting the corresponding puzzle files (those starting with "0002009845") from the Foldit running directory to force a re-download of the puzzle from the server. – All of that might be voodoo, though.

We'll try to keep you updated as we figure out more what the issues might be.

Xartos Lv 1

thx 4 the info. starting after opening another puzzle worked for me at least one time (1st try).

John McLeod Lv 1

In 1986 I published (my only refereed paper) the mathematical basis for James G. Nourse's Configuration Symmetry Group.
https://pubs.acs.org/doi/abs/10.1021/ci00050a009

That was part of the sugars database for automated reaction design in DENDRAL, back in the very early days of chemical AI.

Sorry to be missing this puzzle! Am in discussions to get an actual graphics card for my antique client.

Turns out Microsoft quietly threw my onboard chipset under the bus about 5 years ago. When Foldit's server side's graphics went to OpenGL 3.x it bricked my client as presently configured. Here's the details.

https://forums.intel.com/s/question/0D50P0000490WWlSAM/update-opengl?language=en_US

"That is correct the Intel(R) Q45/Q43 Express Chipset supports OpenGL 2.0 and you will need a system that supports up to 3.0, as Al Hill mentioned above if you have a PCie slot you can buy a graphics card for you system, other than that you will need to buy a new computer to work with this type of software."

me again: That might be the way ahead for Bletchley's legacy client too. Sorry for off-topic ramblings, hope to be back soon :-)

marsfan Lv 1

I have two questions regarding this puzzle.

  1. Some of the fragments have green endpoints sticking off of them. Is there anything special about these?
  2. Often, when I try to change reactant fragments, it will change, but then immediately reverts back to the previous design. Why is this happening?

rmoretti Staff Lv 1

The two green atoms sticking off of some of the reactants are chlorine atoms. A number of drugs and drug-like molecules have chlorine (or fluorine) atoms on them, as they have structural and interaction properties that are different from the other atoms typically in molecules.

I'm not sure what might be happening with the reverting. I will say that selecting the reactants/reagents in the panel only sets them for the proposed (ghost) structure. Until you click the accept button (the two test tubes into a beaker icon), your designed ligand won't be realized in the protein. Exiting out of the panel by the red X close button will discard the proposed structure and return you to the ligand you had when opened the panel.