2062: VHL ligand design: Round 2
|Name:||2062: VHL ligand design: Round 2|
|Expired:||11/03/2021 - 23:00|
|Description:||Design a small molecule which can bind VHL! This is the second 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:
For this round, we're encouraging you to do more to change the core of the compound, specifically the central proline-like five-member ring (pyrrolidine). Changing that group should get you a bonus.
We've also adjusted the objectives to address some issues we saw in round 1. In particular, we've added penalties for enol and enamine groups, which rapidly rearrange in cells. We've also penalized thiocarbonyls. These join the penalty for amide groups and the pyrrolidine in the "Bad Groups" objective. We've also added a cLogP objective to keep the compounds from getting too "greasy", which is bad for drug properties. You'll need to carefully balance removing polar groups to get the TPSA bonus, while not making things too hydrophobic and losing the cLogP bonus.
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.
|Categories:||Overall, Small Molecule Design|
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