puzzle picture
213: Hold Me Tighter
Status: Closed


Name: 213: Hold Me Tighter
Status: Closed
Created: 10/22/2009
Points: 100
Expired: 10/30/2009 - 12:00
Difficulty: Advanced
Description: Have you ever stayed up at night wondering how you can bind biotin in a non-streptavadin protein scaffold? I know I sure have. Well, now you're in luck! With the new and improved "Hold Me Tighter" puzzle (A welcome improvement to the widely popular "Hold Me Tightly" puzzle) you can put those late night thoughts to good use! In this puzzle we have 3 scaffolds to choose from. (When you reset the puzzle, a random scaffold will appear). Scaffold 1: 1cbs: A cellular retionic-acid-binding protein; Scaffold 2: 1igs: A glycerolphosphate synthase; Scaffold 3: 1n9l: A phot-LOV1 domain. 3X the scaffolds equals 3X the fun! Your puzzle score is determined by the best scoring ligand in any of the three scaffolds, so give them all a try. Some scaffolds may be easier than others, but the best score could be in any of them.

Top Groups

21Cedarburg H.S.8,0441
24CSE Grads8,0441

Top Evolvers

21champuli1 75 1437 8,062100
22Guyoni 75 1437 8,06097
23CharlieFortsCon... 75 1437 Contenders8,05793
24Grom 75 1437 Russian team8,05590

Top Soloists

21Mike Cassidy 75 76 Void Crushers8,05545
22Mr_Jolty 75 1437  8,05544
23Sellod 75 1437  8,05542
24Susanne 75 1437 SETI.Germany8,05440
25vakobo 75 727 Russian team8,05438

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Joined: 05/03/2009
Groups: Contenders
Puzzle scoring

It'd clear that this one isn't being scored in a traditional way - is there any chance someone from FoldCentral can give some more details?
Cheers CFC

Joined: 10/10/2008
Groups: None


This puzzle definitely is scored a bit differently, I think I mentioned it briefly in the description of the puzzle, but I should have made it bold or something. Sorry.

Basically, there are three scaffolds in this puzzle. When you reset the puzzle, it randomly chooses one of them. The score that shows up at the top reflects only the score of the ligand from the best scoring scaffold.

There is also a condition which requires that the entire design (including the score of the side chains) needs to be within a certain score (or better) of the original starting structure. This is meant to prevent crazy clashes within the protein which may (for some reason) make the ligand really stable at the cost of the rest of the protein's stability.

Also, the automatic features like mutate all and shake sidechains works on the score of the entire protein. (Some may notice that these features sometimes makes your score worse, that happens when a mutation is found that makes the score of the entire protein better, but makes the ligand score worse).

The goal of all these restrictions is to get the best design that binds that ligand as tight as possible without making the rest of the scaffold too energetically unfavorable. Additionally, the backbone is fixed in place and will not move. This is because the designs (when we actually go and make them) are more reliable when we don't use the backbone movement algorithms.

I hope that clears up the scoring. Let me know if you have any other questions!


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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