2074: VHL ligand design: Round 5
|Name:||2074: VHL ligand design: Round 5|
|Expired:||12/01/2021 - 23:00|
|Description:||Due to issues with objectives, this puzzle has been closed early and is now worth zero competition points. It has been reposted as Puzzle 2074b. All saved solutions from this puzzle can be loaded into the reposted puzzle.
Design a small molecule which can bind VHL! This is the fifth 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, or
For this round, please focus in on changing the center bit of the molecule. The 'Preserve Structure' objective gives a big bonus if you keep the three-member ring and the linked five and six member rings - leave these end bits alone and change up the bits in between. The 'Alter Core' objective will give a big bonus if you change up the central five-member ring.
Also making an appearance this round are two structural waters. We hope that putting these waters in explicitly will help with maintaining some key interactions to the protein. Also for this purpose is the HBond objective, which identifies the six hydrogen bonding atoms on the protein (and waters) which the starting ligand makes contact to. Their ligand partners can be changed, but another ligand atom should take their place.
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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