Foldit
Encyclopedia
Foldit is an online
puzzle video game about protein folding
. The game is part of an experimental research project, and is developed by the University of Washington
's Center for Game Science in collaboration with the UW Department of Biochemistry
. The objective of the game is to fold the structure of selected proteins to the best of the player's ability, using various tools provided within the game. The highest scoring solutions are analysed by researchers, who determine whether or not there is a native structural configuration (or native state
) that can be applied to the relevant proteins, in the "real world". Scientists can then use such solutions to solve "real-world" problems, by targeting and eradicating diseases, and creating biological innovations.
, a protein research scientist at the University of Washington, is responsible for beginning the Foldit project. Prior to the project's commencement, Baker and his laboratory relied upon another research project, Rosetta, to predict the native structures of various proteins, using special computer protein structure prediction
algorithms. The project was eventually extended to utilize the processing power of user's personal computers, by developing a distributed computing
program; Rosetta@home
. The Rosetta@home program was made available for public download
, and was designed to display progress of a particular protein being worked on at the time, as a screensaver
. The results of the program's prediction routines are sent to a central project server
, for verification.
Some users of Rosetta@home became frustrated with the program, when they realised they could see ways of solving the protein structures
themselves, but could not interact with the program. When Baker realised that humans could have considerable potential over computers attempting to solve protein structures, he approached David Salesin, a fellow computer scientist, and Zoran Popović, a game designer studying at the same university, to help conceptualize and build an interactive program that would both appeal to the public, and assist in their efforts to find the native structures of proteins - a game.
In 2008, the Foldit project submitted solutions to the Critical Assessment of Techniques for Protein Structure Prediction
(CASP) contest. The results were announced in early 2009.
In 2011, players of Foldit helped to decipher the crystal structure
of the Mason-Pfizer monkey virus (M-PMV) retroviral
protease
, an AIDS
-causing monkey virus
. While the puzzle was available to play for a period of three weeks, players produced an accurate 3D
model of the enzyme
in just ten days. The problem of how to configure the structure of the enzyme had stumped scientists for 15 years.
, is reasonably well understood, as is the means by which proteins are encoded as DNA
. Determining how the primary structure of a protein turns into a functioning three-dimensional structure—how the molecule
"folds"—is more difficult; the general process is known, but protein structure prediction is computation
ally demanding.
Foldit is an attempt to apply the human brain
's natural three-dimensional pattern matching
abilities to this problem. Current puzzles are based on well-understood proteins; by analysing the ways in which humans intuitively approach these puzzles, researchers hope to improve the algorithms employed by existing protein-folding software.
and distributed computing.
Foldit provides a series of tutorial
s in which the user manipulates simple protein-like structures, and a periodically updated set of puzzles based on real proteins. The application displays a graphical representation of the protein's structure which the user is able to manipulate with the aid of a set of tools.
As the structure is modified, a "score" is calculated based on how well-folded the protein is, and a list of high scores for each puzzle is maintained. Foldit users may create and join groups, and share puzzle solutions with each other; a separate list of group high scores is maintained.
ONLINE
ONLINE is a magazine for information systems first published in 1977. The publisher Online, Inc. was founded the year before. In May 2002, Information Today, Inc. acquired the assets of Online Inc....
puzzle video game about protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
. The game is part of an experimental research project, and is developed by the University of Washington
University of Washington
University of Washington is a public research university, founded in 1861 in Seattle, Washington, United States. The UW is the largest university in the Northwest and the oldest public university on the West Coast. The university has three campuses, with its largest campus in the University...
's Center for Game Science in collaboration with the UW Department of Biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
. The objective of the game is to fold the structure of selected proteins to the best of the player's ability, using various tools provided within the game. The highest scoring solutions are analysed by researchers, who determine whether or not there is a native structural configuration (or native state
Native state
In biochemistry, the native state of a protein is its operative or functional form. While all protein molecules begin as simple unbranched chains of amino acids, once completed they assume highly specific three-dimensional shapes; that ultimate shape, known as tertiary structure, is the folded...
) that can be applied to the relevant proteins, in the "real world". Scientists can then use such solutions to solve "real-world" problems, by targeting and eradicating diseases, and creating biological innovations.
Rosetta
David BakerDavid Baker (biochemist)
David Baker is an American biochemist and computational biologist who studies methods to predict the three-dimensional structures of proteins. He is a Professor of Biochemistry at the University of Washington, where he is the principal investigator of the 30+ member...
, a protein research scientist at the University of Washington, is responsible for beginning the Foldit project. Prior to the project's commencement, Baker and his laboratory relied upon another research project, Rosetta, to predict the native structures of various proteins, using special computer protein structure prediction
Protein structure prediction
Protein structure prediction is the prediction of the three-dimensional structure of a protein from its amino acid sequence — that is, the prediction of its secondary, tertiary, and quaternary structure from its primary structure. Structure prediction is fundamentally different from the inverse...
algorithms. The project was eventually extended to utilize the processing power of user's personal computers, by developing a distributed computing
Distributed computing
Distributed computing is a field of computer science that studies distributed systems. A distributed system consists of multiple autonomous computers that communicate through a computer network. The computers interact with each other in order to achieve a common goal...
program; Rosetta@home
Rosetta@home
Rosetta@home is a distributed computing project for protein structure prediction on the Berkeley Open Infrastructure for Network Computing platform, run by the Baker laboratory at the University of Washington...
. The Rosetta@home program was made available for public download
Uploading and downloading
In computer networks, to download means to receive data to a local system from a remote system, or to initiate such a data transfer. Examples of a remote system from which a download might be performed include a webserver, FTP server, email server, or other similar systems...
, and was designed to display progress of a particular protein being worked on at the time, as a screensaver
Screensaver
A screensaver is a type of computer program initially designed to prevent phosphor burn-in on CRT and plasma computer monitors by blanking the screen or filling it with moving images or patterns when the computer is not in use...
. The results of the program's prediction routines are sent to a central project server
Server (computing)
In the context of client-server architecture, a server is a computer program running to serve the requests of other programs, the "clients". Thus, the "server" performs some computational task on behalf of "clients"...
, for verification.
Some users of Rosetta@home became frustrated with the program, when they realised they could see ways of solving the protein structures
Protein structure
Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...
themselves, but could not interact with the program. When Baker realised that humans could have considerable potential over computers attempting to solve protein structures, he approached David Salesin, a fellow computer scientist, and Zoran Popović, a game designer studying at the same university, to help conceptualize and build an interactive program that would both appeal to the public, and assist in their efforts to find the native structures of proteins - a game.
Foldit
Many of the same people who created Rosetta@home, worked on the construction of Foldit. The public beta version was released in May 2008.In 2008, the Foldit project submitted solutions to the Critical Assessment of Techniques for Protein Structure Prediction
CASP
CASP, which stands for Critical Assessment of Techniques for Protein Structure Prediction, is a community-wide, worldwide experiment for protein structure prediction taking place every two years since 1994...
(CASP) contest. The results were announced in early 2009.
In 2011, players of Foldit helped to decipher the crystal structure
Crystal structure
In mineralogy and crystallography, crystal structure is a unique arrangement of atoms or molecules in a crystalline liquid or solid. A crystal structure is composed of a pattern, a set of atoms arranged in a particular way, and a lattice exhibiting long-range order and symmetry...
of the Mason-Pfizer monkey virus (M-PMV) retroviral
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
, an AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
-causing monkey virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
. While the puzzle was available to play for a period of three weeks, players produced an accurate 3D
3D computer graphics
3D computer graphics are graphics that use a three-dimensional representation of geometric data that is stored in the computer for the purposes of performing calculations and rendering 2D images...
model of the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
in just ten days. The problem of how to configure the structure of the enzyme had stumped scientists for 15 years.
Goals
The process by which living beings create the primary structure of proteins, protein biosynthesisProtein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
, is reasonably well understood, as is the means by which proteins are encoded as DNA
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
. Determining how the primary structure of a protein turns into a functioning three-dimensional structure—how the molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
"folds"—is more difficult; the general process is known, but protein structure prediction is computation
Computation
Computation is defined as any type of calculation. Also defined as use of computer technology in Information processing.Computation is a process following a well-defined model understood and expressed in an algorithm, protocol, network topology, etc...
ally demanding.
Foldit is an attempt to apply the human brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
's natural three-dimensional pattern matching
Pattern matching
In computer science, pattern matching is the act of checking some sequence of tokens for the presence of the constituents of some pattern. In contrast to pattern recognition, the match usually has to be exact. The patterns generally have the form of either sequences or tree structures...
abilities to this problem. Current puzzles are based on well-understood proteins; by analysing the ways in which humans intuitively approach these puzzles, researchers hope to improve the algorithms employed by existing protein-folding software.
Methods
Foldit is a combination of crowdsourcingCrowdsourcing
Crowdsourcing is the act of sourcing tasks traditionally performed by specific individuals to a group of people or community through an open call....
and distributed computing.
Foldit provides a series of tutorial
Tutorial
A tutorial is one method of transferring knowledge and may be used as a part of a learning process. More interactive and specific than a book or a lecture; a tutorial seeks to teach by example and supply the information to complete a certain task....
s in which the user manipulates simple protein-like structures, and a periodically updated set of puzzles based on real proteins. The application displays a graphical representation of the protein's structure which the user is able to manipulate with the aid of a set of tools.
As the structure is modified, a "score" is calculated based on how well-folded the protein is, and a list of high scores for each puzzle is maintained. Foldit users may create and join groups, and share puzzle solutions with each other; a separate list of group high scores is maintained.
See also
- Biomolecular structure
- Citizen scienceCitizen scienceCitizen science is a term used for the systematic collection and analysis of data; development of technology; testing of natural phenomena; and the dissemination of these activities by researchers on a primarily avocational basis...
- Disulfide bondDisulfide bondIn chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
- EteRNAEteRNAEteRNA is a browser based game, developed by scientists at Carnegie Mellon University and Stanford University, that engages users to solve puzzles related to the folding of RNA molecules...
- Folding@homeFolding@homeFolding@home is a distributed computing project designed to use spare processing power on personal computers to perform simulations of disease-relevant protein folding and other molecular dynamics, and to improve on the methods of doing so...
- Homology modelingHomology modelingHomology modeling, also known as comparative modeling of protein refers to constructing an atomic-resolution model of the "target" protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein...
- Human-based computation gameHuman-based computation gameA human-based computation game or game with a purpose is a human-based computation technique in which a computational process performs its function by outsourcing certain steps to humans in an entertaining way. This approach uses differences in abilities and alternative costs between humans and...
- Hydrogen bondHydrogen bondA hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
- Lattice proteinLattice proteinLattice proteins are highly simplified computer models of proteins which are used to investigate protein folding.Because proteins are such large molecules, there are severe computational limits on the simulated timescales of their behaviour when modeled in all-atom detail...
- Macromolecular docking
- Modelling biological systems
- Molecular dynamicsMolecular dynamicsMolecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
- Molecular graphicsMolecular graphicsMolecular graphics is the discipline and philosophy of studying molecules and their properties through graphical representation. IUPAC limits the definition to representations on a "graphical display device"...
- Molecular modellingMolecular modellingMolecular modelling encompasses all theoretical methods and computational techniques used to model or mimic the behaviour of molecules. The techniques are used in the fields of computational chemistry, computational biology and materials science for studying molecular systems ranging from small...
- Molecular modelling software
- Peptide bondPeptide bondThis article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
- Protein designProtein designProtein design is the design of new protein molecules, either from scratch or by making calculated variations on a known structure. The use of rational design techniques for proteins is a major aspect of protein engineering....
- Protein engineeringProtein engineeringProtein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles....
- Protein structure prediction software
- ProteomicsProteomicsProteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
- Serious gameSerious gameA serious game is a game designed for a primary purpose other than pure entertainment. The "serious" adjective is generally prepended to refer to products used by industries like defense, education, scientific exploration, health care, emergency management, city planning, engineering, religion,...
- Structural alignmentStructural alignmentStructural alignment attempts to establish homology between two or more polymer structures based on their shape and three-dimensional conformation. This process is usually applied to protein tertiary structures but can also be used for large RNA molecules...
- Structural bioinformaticsStructural bioinformaticsStructural bioinformatics is the branch of bioinformatics which is related to the analysis and prediction of the three-dimensional structure of biological macromolecules such as proteins, RNA, and DNA...
- X-ray crystallographyX-ray crystallographyX-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...