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1503: Y1 Receptor - Dock the ligand!

Closed since almost 8 years ago

Intermediate Overall

Summary

Created
April 03, 2018
Expires
Max points
100
Description

This is a ligand docking puzzle. Instead of changing the protein, we'd like you to focus on finding the best position and interactions for the ligand. (The residue in the middle of the alpha helices, currently making a number of clashes.)

This is a follow-up puzzle of 1441 and 1446. Like 1446, we're asking you to place a known binder to the human Y1 neuropeptide receptor into its binding site. Like 1446, this is ligand is BIBP-3226. In this puzzle, though, we're giving you a different protein structure.

We think the backbone of the binding site of this model is pretty close to the actual structure, so we're fixing the backbone. Focus on placing the ligand and optimizing the interactions of the ligand with the side-chains.

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Comments

LociOiling Lv 1

See the comments for Puzzle 1446 for background on what's going on.

In puzzle 1503, the ligand at segment 321 is the designer molecule BIBP-3226. Similar to protein sidechains, it has multiple rotamers, different shapes or positions it can take.

In the selection interface you can select the ligand, the move through the rotamers using the left and right arrow keys.

The protein backbone in puzzle 1503 is all locked, but many of the protein sidechains can move. Since backbone is locked, remix and rebuild won't work, but shake and wiggle will.

Here's what the ligand looks like in a JMol (a molecule viewer):

[img_assist nid=2004438 title=BIBP-3226 seen in JMol desc=The ligand in puzzle 1503 is the designer molecule BIBP-3226. link=node align=left width=640 height=457]



Here's a similar pose seen in Foldit:

[img_assist|nid=2004439|title=BIBP-3226 seen in Foldit.|desc=|link=node|align=left|width=640|height=457]


You may notice that there are a few spots where JMol shows double bonds where Foldit has a single bond, and vice versa. The scientists have said that this is something to with how Foldit shows resonances, cases where there aren't quite enough electrons go around. Check out resonance (chemistry) on wikipedia for more.

LociOiling Lv 1

Here's the version with atom numbers, as originally seen in the puzzle 1446 comments.

[img_assist nid=2004447 title=BIBP-3226 atom numbers. desc= link=node align=left width=640 height=457]

Bletchley Park Lv 1

Is there a scoring logic (scoring rules ?) behind the various different interactions that the ligand can meke with the rest? I wonder if some connections are favored over others based solely on which sidechain interacts with which atoms, thus being scored differently.

Clashing, voids and other factors will likely play a role too.