Information about the objectives in this puzzle. (All objectives give +1000 points when fully satisfied.)
Most objectives have a "Show" button which should highlight areas of concern in red.
The amide penalty seems to be only 2.5 points per amide.
There are three amides when the puzzle starts. If you remove one of the oxygens from those amides, the amide penalty score changes from 992.25 to 995.
Zapping two more oxygens gets you to the full 1000 point bonus.
Is this as intended? It seems like a deduction of 25 or even 250 points would be more typical.
Larger benefit associated with amide removal would make sense in context of providing diverse, potentially more useful E3 ligase binders for use in PROTACS (e.g. with better potential for good DMPK properties).
Yeah, where we set the levels for the bonuses is something we'll have to figure out. The plan is to run several rounds of the VHL ligand design puzzles, with different settings for the bonuses. We'll take a look at the structures coming out of the first round and see if we need to adjust things.
One consideration is that we don't necessarily want to encourage people to make poor binders in the goal to remove amides. A deduction of 250 points would likely promote people to remove all the amides, even if that makes a poor binder. We need to balance the penalties to strike the right trade-off. With later rounds we'll be able to dial that in better, but for the first round we tried to be somewhat conservative.