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2079: VHL ligand design: Round 6
Status: Closed
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Summary
| Name: |
2079: VHL ligand design: Round 6 |
| Status: |
Closed |
| Created: |
12/08/2021 |
| Points: |
100 |
| Expired: |
12/15/2021 - 23:00 |
| Difficulty: |
Intermediate |
| Description: |
Design a small molecule which can bind VHL! This is the sixth in a series of puzzles using the small molecule design tools to design small molecule binders to the von Hippel-Lindau E3 ubiquitin ligase. We don't want you to modify the protein, but instead we'd like you to build new small molecules which fit into the VHL pocket. See the new "Inside the Pocket" and "Fun with Fragments!" tutorials to learn how to use the small molecule design tools.
Note: To get the most out of the small molecule design tools, we recommend changing you view settings to the Small Molecule Design Preset
We saw some interesting designs in Round 5(b). Round 6 is very similar. We're still asking you to focus on changing the central five-member ring with the attached red oxygen as well as removing the attached amide group, while maintaining the existing hydrogen bonding interactions. Round 6 has a tighter TPSA penalty and a more relaxed cLogP penalty. Drug design is a balancing act, and we hope this new balance between these two competing objectives will be more helpful. We've also made the rotatable bond penalty more stringent -- the center hydroxyl OH is likely to be most useful if it's attached to something like a rigid ring, rather than groups which have rotatable bonds.
You should be able to load existing solutions from Round 5 and Round 5b into this puzzle to further refine them.
This is a project in collaboration with Boehringer Ingelheim. Boehringer Ingelheim has committed to help evaluate and test the molecules which Foldit players have designed. All compounds created as part of the collaboration puzzles will be made publicly available. Experimental results from testing the molecules will also be released publicly. All participants and game sponsors of current and future small molecule design games commit to complying with the Foldit Terms of Service including those pertaining to intellectual property.
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| Categories: | Overall, Small Molecule Design |
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Information about the objectives in this puzzle. (All objectives give +1000 points when fully satisfied, for a maximum of +10 000.)
Most objectives have a "Show" button which should highlight areas of concern in red. (Even when fully satisfied, objectives may highlight groups which may eventually contribute.)