Anfinsen's dogma
Encyclopedia
Anfinsen's dogma is a postulate in molecular biology
championed by the Nobel Prize
Laureate Christian B. Anfinsen
. The dogma states that, at least for small globular proteins, the native structure
is determined only by the protein's amino acid
sequence
.
This amounts to say that, at the environmental conditions (temperature, solvent concentration and composition, etc.) at which folding occurs, the native structure is a unique, stable and kinetically accessible minimum of the free energy.
The three conditions:
uniqueness: requires that the sequence does not have any other configuration with a comparable free energy. Hence the free energy minimum must be unchallenged.
stability: small changes in the surrounding environment cannot give rise to changes in the minimum configuration. This can be pictured as a free energy surface that looks rather like a funnel (with the native state in the bottom of it) than like a soup plate; the free energy surface around the native state must be rather steep and high, in order to provide stability.
kinetical accessibility: means that the path in the free energy surface from the unfolded to the folded state must be reasonably smooth or, in other words, that the folding of the chain must not involve highly complex changes in the shape (like knots or other high order conformations).
How the protein reaches this structure is the subject of the field of protein folding
, which has a related dogma called Levinthal's paradox. The Levinthal paradox states that the number of possible conformations available to a given protein is astronomically large, such that even a small protein of 100 residues would require more time than the universe has existed to explore all possible conformations (1026 seconds) and choose the appropriate one, it would also arguably make computational prediction of protein structures under the same basis unfeasible if not impossible.
Also, some proteins need the assistance of another protein called a chaperone protein to fold properly. It has been suggested that this disproves Anfinsen's dogma. However, the chaperones do not appear to affect the final state of the protein; they seem to work primarily by preventing aggregation of several protein molecules before the protein is folded.
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
championed by the Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
Laureate Christian B. Anfinsen
Christian B. Anfinsen
Christian Boehmer Anfinsen, Jr. was an American biochemist. He shared the 1972 Nobel Prize in Chemistry with Stanford Moore and William Howard Stein for work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation...
. The dogma states that, at least for small globular proteins, the native structure
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...
is determined only by the protein's amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
.
This amounts to say that, at the environmental conditions (temperature, solvent concentration and composition, etc.) at which folding occurs, the native structure is a unique, stable and kinetically accessible minimum of the free energy.
The three conditions:
uniqueness: requires that the sequence does not have any other configuration with a comparable free energy. Hence the free energy minimum must be unchallenged.
stability: small changes in the surrounding environment cannot give rise to changes in the minimum configuration. This can be pictured as a free energy surface that looks rather like a funnel (with the native state in the bottom of it) than like a soup plate; the free energy surface around the native state must be rather steep and high, in order to provide stability.
kinetical accessibility: means that the path in the free energy surface from the unfolded to the folded state must be reasonably smooth or, in other words, that the folding of the chain must not involve highly complex changes in the shape (like knots or other high order conformations).
How the protein reaches this structure is the subject of the field of 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....
, which has a related dogma called Levinthal's paradox. The Levinthal paradox states that the number of possible conformations available to a given protein is astronomically large, such that even a small protein of 100 residues would require more time than the universe has existed to explore all possible conformations (1026 seconds) and choose the appropriate one, it would also arguably make computational prediction of protein structures under the same basis unfeasible if not impossible.
Also, some proteins need the assistance of another protein called a chaperone protein to fold properly. It has been suggested that this disproves Anfinsen's dogma. However, the chaperones do not appear to affect the final state of the protein; they seem to work primarily by preventing aggregation of several protein molecules before the protein is folded.
See also
- POEM@HomePOEM@HomePOEM@Home is a distributed computing project hosted by the Karlsruhe Institute of Technology and running on the Berkeley Open Infrastructure for Network Computing software platform...
is a distributed computingDistributed computingDistributed 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...
project that is based on Anfinsen's dogma. - Discovery of PCAIN provides compelling evidence in support of Anfinsen's Dogma