Foldit Puzzles

1443: Classroom Puzzle: Engineer the Active Site

How enzymes catalyze reactions is still an ongoing debate in the biochemistry literature. Some people think it's most important that the active site provides the right chemical environment, others that the geometry be perfected, and others that think that the motions of the protein are most important. This puzzle is meant to allow you to try and design the active site to make the best possible enzyme. One way to improve an enzyme's activity is by binding the transition state of the reaction tighter. In this puzzle, we've put a transition-state analog into the active site, and would like you to try and improve the binding to that analog by redesigning the active site residues!

1440: Aflatoxin Challenge: Round 1

Aflatoxins are a class of poisonous compounds that contaminate a significant portion of the global food supply. In this puzzle, players are challenged to redesign an enzyme that could break down aflatoxin molecules. The majority of the protein is frozen, with the aflatoxin ligand fixed in a binding pocket. Surrounding the binding pocket are a number of loops that might be redesigned without affecting the folding stability of the protein. In these loops, players may manipulate the protein backbone and mutate the residue sidechains. Redesign the loops of this protein to better bind the aflatoxin ligand!

1438: Unsolved De-novo Freestyle 118

Chikungunya (CHIK-un-goon-ya) virus (also known as CHIKV) is a mosquito-transmitted alphavirus that has spread around the world and is currently infecting people in about 60 countries globally. CHIKV is rarely fatal, but causes severe joint pain for months to years that can debilitate affected patients for long periods of time. There are currently no known drugs to treat CHIKV infection, primarily due to a lack of understanding of the structure of CHIKV proteins involved in viral genome replication. The Geiss lab has worked on developing drug targeting the membrane bound CHIKV nsP1 protein, which is the anchor for the viral genome replication complex on cellular membranes and a multifunctional enzyme that forms a 5’ RNA cap structure on the end of the CHIKV RNA genome. Solving the structure of the CHIKV nsP1 protein would provide critical information for designing drugs that inhibit nsP1 function and abort viral genome replication.

1442: Sketchbook Puzzle - Revisiting Puzzle 136

This small protein interferes with cellular adhesion and, consequently, clotting mechanisms. In this experimental puzzle you will have 250 moves at your disposal. Once you use them up, you can reset and try something else!

1441: Y1 Receptor Homology Modeling

The neuropeptide Y receptors are a group of human cell surface receptors found in the brain and digestive system, and are involved in regulating hunger and satiety. A better understanding of the neuropeptide Y receptors could allow scientists to better understand the diseases and disorders which involve misregulation of hunger and satiety. Treatment of obesity is the obvious example, but there are other disorders characterized by a mis-regulation of hunger (such as Prader-Willi syndrome). Chemotherapy is often associated with appetite suppression, so a treatment which can increase hunger could help reduce the dangerous weight loss sometimes seen in chemotherapy patients.

1439: Classroom Puzzle: Chaperone Folding

How chaperones help proteins to fold is still a matter of great debate in the scientific literature. This Classroom puzzle will help students explore different possible ways that a chaperone can interact with its client proteins. The puzzle includes a frozen chaperone protein—a miniaturized version of GroEL that can perform some of the functions of the full GroEL chaperone. The folding client is barnase, an well-behaved bacterial protein that is a popular model in protein folding studies. Players can choose to start with barnase in either the folded or unfolded state. To switch between the folded and unfolded starts, reset the puzzle (see the Actions menu in Original Interface; or the Undo menu in Selection Interface). It will be up to you to determine what provides the optimal balance between folding and interaction with the chaperone!

1437: Small Monomer Design

This puzzle challenges players to design a single-chain protein with 65-75 residues. We've softened the penalties associated with the Core Existence filter, which have typically been very steep. The starting structure has 65 residues, but more can be added at a cost of 16 points per residue. See the puzzle comments for filter details. The Baker Lab will run folding predictions on your solutions for this puzzle, and those that perform well will be synthesized in the lab. Remember, you can use the Upload for Scientists button for up to 5 designs that you want us to look at, even if they are not the best-scoring solutions!

1436: NMN Binder Design: Round 2

This is a followup to Puzzle 1422. Redesign the loops of this protein to better bind the ligand! Nicotinamide mononucleotide (NMN) is a small-molecule that makes up part of the small-molecule nicotinamide adenine dinucleotide (NAD), which is sometimes regarded as 'the molecule of youth.' Scientists know that the amount of NAD in our cells declines as we age, and so designing a protein to bind to NMN is the first step towards achieving protein-based biosensors that can detect NMN levels in cells. Such biosensors would help scientists to understand the aging process and could potentially lead to a 'cure' for aging! In this puzzle, players have a little more freedom in redesigning the NMN binding pocket. Players may load in solutions from Puzzle 1422.

1431: Unsolved De-novo Freestyle 117

Note: In response to some player feedback related to the excessive size of this protein, we're extending the puzzle deadline by two weeks! The puzzle will expire on October 9 at 23:00 UTC.

1435: Extra Large Monomer Design

This puzzle challenges players to design a single-chain protein with 95-120 residues. We've softened the penalties associated with the Core Existence and Residue Count filters, which have typically been very steep. The starting structure has 95 residues, but more can be added at a cost of 16 points per residue. See the puzzle comments for filter details. The Baker Lab will run folding predictions on your solutions for this puzzle, and those that perform well will be synthesized in the lab. Remember, you can use the Upload for Scientists button for up to 5 designs that you want us to look at, even if they are not the best-scoring solutions!