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2074b: VHL ligand design: Round 5b
Status: Closed

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rmoretti's picture
User offline. Last seen 1 hour 22 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, for a maximum of +10 000.)

  • Alter Core - A large bonus for changing up the central five-member-ring with a hydroxyl oxygen. (Click "Show" to highlight the ring at issue.)
  • HBond - A large bonus for preserving all the existing hydrogen bonding contacts of the starting ligand. (Click "Show" to highlight the atom needing the hydrogen bond.)
  • 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. (Click "Show" to highlight groups at issue.)
  • Ligand cLogP - A measure of polarity - Keeps the molecule from getting too hydrophobic. To improve, try adding polar oxygens and nitrogens.
  • Ligand TPSA - Topological Polar Surface Area - Keeps the polar surface area (including buried polar surface) low. To improve, try removing oxygens and nitrogens.
  • 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.)

Aubade01's picture
User offline. Last seen 55 min 13 sec ago. Offline
Joined: 10/12/2013
Groups: None
Another charged species

The program is allowing the formation of a sulfonium ion similar to the ammonium ion previously reported.

On the thiazole, substitute the sulfur with nitrogen to form an imidazole. Then substitute this nitrogen back to sulfur again. You will now have a valid charged sulfonium ion (a protonated sulfur) species. There is no immediate undesired group penalty for doing this as there now is for ammonium ion formation. The hydrogen can be selected, but not deleted. It can also be replaced with carbon to methylate the sulfur. This does give an undesired group penalty.

>>>>> Aubade00/01

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