FoldIt

We have more than 100,000 types of protein in our bodies alone. Though the primary structure of the proteins can be easily deduced (both by sequencing and using the genetic code) the functional three-dimensional structure prediction arising from folding —is more computationally demanding. There are many diseases caused by misfolding of protein are aplenty- cystic fibrosis (misfolded CFTR protein), Marfan syndrome (misfolded fibrillin), Fabry disease (misfolded alpha galactosidase). They may also be the reason for some cancers due to ineffective functioning, of tumour suppressor proteins such as von Hippel Lindau protein or p53.

Thus it is almost impossible for the scientific community which is small relative to the growing number of population and the fatal diseases to find a solution for this.

Recently thanks to cyberspace the key to unlock the innumerable cures to the vast diseases maybe found by a 13 year old video gamer who has never heard of whatsoever never heard of protein steric hindrances or anything about protein folding.

WHAT???

Everybody wants to have high scores in the games they play. And also humans have puzzle-solving intuitions that are absent in computers .FoldIt an online puzzle video game about protein folding exploits these aspects. Here the gamers analyse the problem of proteins, theirs structures, folding as game.

Stage 1:

Download FoldIt (free).

Read the rules.

Warm yourself up through a series of tutorials in which simple protein-like structures based on real proteins are manipulated with the aid of a set of tools

Stage 2:

Manipulate amino acid chains starting simple with "One Small Clash," through "Rubber Band Reversal. The application displays a graphical representation of the protein's structure. The objective is to fold the structure of proteins . When the energy required  in maintaining the molecule in a particular shape drops it is closer to original protein structure. This increases the player’s score increases.
Stage 3:
The Real Deal- Facing the unknown Demon.
A problem based on proteins whose folding and 3D structures are yet unknown is posed on the website and thousands of players compete to see who can find the best solution. There is fierce competition to see who could come up with the best solution (based on how well the different structural pieces of the protein fit together).  The highest scoring solutions are analysed by researchers, who determine whether or not such a native structural configuration exists.
Thus by analysing different” high scored” models generated by the gamers the scientists may actually find the real model.

High Scorers:
FoldIt helped to decipher the crystal structure of the Mason-Pfizer monkey virus (M-PMV) retroviralprotease, an AIDS-causing monkey virus. This is a key enzyme in the production of a mature virus and so developing drugs using this structure could be useful in developing an HIV therapy. The interpretation of the x-ray data of the protein to give the final 3D structure could not be done. FoldIt players (FoldIt Contenders Group and FoldIt Void Crushers Group, spvincent, grabhorn, mimi) optimized the 3D model, based on an NMR structure in just ten days.  The top groups were listed as co-authors by their team name in the publication (This was a problem which had frustrated scientists for 15 years. But FoldIt game has solved it in 10 days)
There are tools for players to encode their folding strategies as “recipes” and to share their recipes with other players, who are able to further modify and redistribute them. Through this Players developed over 5,400 different recipes. The most successful recipes rapidly spread through the FoldIt player population, and two of the recipes became particularly dominant. Examination of these two recipes revealed a striking similarity to an unpublished algorithm developed by scientists over the same period.

The FoldIt Void Crushers group improved a structure generated by the Rosetta Server to generate a near-native conformation of Pseudomonas aeruginosa protein T0581

FoldIt has four publications and a host of puzzles left to solve from deadly diseases to bio fuels, FoldIt has proven that the concept, "creativity isn't constrained by what they think a correct answer should look like” Thus the creative nature of individuals with no academic background on biochemistry has helped in unlocking the problems on biomoleucles

New Games:

EteRNA- folding of RNA molecules for designing RNA based nanomachines (more on NanoDNA and NanoRNA in my following blog entries)

Phylo - determine the most likely nucleotide sequence of each species by comparing the sequences of children species with those of a most recent common ancestor.