puzzle picture
2068: VHL ligand design: Round 3
Status: Closed

Soloists



Need this puzzle? Log in to download.  

Comments

rmoretti's picture
User offline. Last seen 1 day 28 min ago. Offline
Joined: 01/15/2010
Groups: Foldit Staff
Objective Information

Information about the objectives in this puzzle. (All objectives give +1000 points when fully satisfied.)

  • HBond - A large bonus for making a hydrogen bond to the serine in the center of the pocket. (Click "Show" to highlight the atom needing the hydrogen bond.)
  • Buried Unsats - Penalizes polar atoms that cannot make hydrogen bonds
  • Bad Groups - Gives a bonus for avoiding groups we're interested in removing, including enol, enamine, thiocarbonyl, hydroxylamines, geminal diols, charged nitrogens, and alpha-beta unsaturated carbonyls.
  • Ligand cLogP - A measure of polarity - Keeps the molecule from getting too hydrophobic
  • Ligand TPSA - Topological Polar Surface Area - Keeps the polar surface area (including buried polar surface) low.
  • Ligand Hydrogen Bond Donors - Keep the number of ligand hbond donors low.
  • Molecular Weight - Intended to keep the ligand from getting too big.
  • Number of Rotatable Bonds - Intended to keep the ligand from getting too big and floppy.
  • Ligand Substructure - Identify areas of the small molecule which aren't very drug-like.
  • Synthetic Accessibility - Identify molecules which are likely to be hard to make in the lab.

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.)

alcor29's picture
User offline. Last seen 7 hours 10 min ago. Offline
Joined: 11/16/2012
bonds to protein?

Guessing from your view settings, making bonds from the ligand to the protein is not important?

alcor29's picture
User offline. Last seen 7 hours 10 min ago. Offline
Joined: 11/16/2012
nvm

I guess the sheet bonds will take care of it.

alcor29's picture
User offline. Last seen 7 hours 10 min ago. Offline
Joined: 11/16/2012
and.....

there's the serine you mentioned. Duh.

rmoretti's picture
User offline. Last seen 1 day 28 min ago. Offline
Joined: 01/15/2010
Groups: Foldit Staff
Serine sidechain to ligand hbond.

In case it's still unclear, the Objective should pick up the hydrogen bond between the serine sidechain to the ligand. (There's some existing hydrogen bonds between that serine and other protein residues, but the bonus should be specific to forming a new hydrogen bond to that serine sidechain.)

To locate the serine, you can click the "Show" of the HBond objective. That should label the sidechain hydroxyl which needs the hbond with a red glow. (Look at the bottom middle of the pocket.)

Aubade01's picture
User offline. Last seen 1 day 22 hours ago. Offline
Joined: 10/12/2013
Groups: None
Client Crash

Adding a nitrogen in close proximity to the protein bound imidazole causes the client to crash and disappear.
Windows 10. Crash repeated.

>>>>> Aubade00/01

rmoretti's picture
User offline. Last seen 1 day 28 min ago. Offline
Joined: 01/15/2010
Groups: Foldit Staff
Share with scientists?

If you could share with scientists the particular structure which causes the crash, that would help. (It's often the details about the particular structure you generated which results in issues.)

Aubade01's picture
User offline. Last seen 1 day 22 hours ago. Offline
Joined: 10/12/2013
Groups: None
CRASH STRUCTURE

This structure has been uploaded.

The tertiary methyl group on the left side has a methyl proximate to the imidazole. Substituting the right and downward hydrogen with nitrogen gives a crash on my system.

>>>>> Aubade00/01

alcor29's picture
User offline. Last seen 7 hours 10 min ago. Offline
Joined: 11/16/2012
Crashy

Very crashy again. 3 or 4 times already this morning. Hard to work this way. Will allow one more crash and then done with 2068. Sorry can't find log since running multiple clients.

(It would be nice to run separate logs for each client. )

User login
Download links:
  Windows    OSX    Linux  
Windows
(7/8/10)
OSX
(10.12 or later)
Linux
(64-bit)

Are you new to Foldit? Click here.

Are you a student? Click here.

Are you an educator? Click here.
Social Media


Search
Only search fold.it
Other Games: Mozak
Recommend Foldit
Topics
Top New Users
Sitemap

Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons