Chou-Fasman method
Encyclopedia
The Chou–Fasman method are an empirical technique for the prediction
of secondary structure
s in protein
s, originally developed in the 1970s. The method is based on analyses of the relative frequencies of each amino acid
in alpha helices
, beta sheet
s, and turns
based on known protein structure
s solved with X-ray crystallography
. From these frequencies a set of probability parameters were derived for the appearance of each amino acid in each secondary structure type, and these parameters are used to predict the probability
that a given sequence of amino acids would form a helix, a beta strand, or a turn in a protein. The method is at most about 50–60% accurate in identifying correct secondary structures, which is significantly less accurate than the modern machine learning
–based techniques.
, glutamate, leucine
, and methionine
were identified as helix formers, while proline
and glycine
, due to the unique conformational properties of their peptide bond
s, commonly end a helix. The original Chou–Fasman parameters were derived from a very small and non-representative sample of protein structures due to the small number of such structures that were known at the time of their original work. These original parameters have since been shown to be unreliable and have been updated from a current dataset, along with modifications to the initial algorithm.
The Chou–Fasman method takes into account only the probability that each individual amino acid will appear in a helix, strand, or turn. Unlike the more complex GOR method
, it does not reflect the conditional probabilities of an amino acid to form a particular secondary structure given that its neighbors already possess that structure. This lack of cooperativity increases its computational efficiency but decreases its accuracy, since the propensities of individual amino acids are often not strong enough to render a definitive prediction.
Turns are also evaluated in four-residue windows, but are calculated using a multi-step procedure because many turn regions contain amino acids that could also appear in helix or sheet regions. Four-residue turns also have their own characteristic amino acids; proline
and glycine
are both common in turns. A turn is predicted only if the turn probability is greater than the helix or sheet probabilities and a probability value based on the positions of particular amino acids in the turn exceeds a predetermined threshold. The turn probability p(t) is determined as:
where j is the position of the amino acid in the four-residue window. If p(t) exceeds an arbitrary cutoff value (originally 7.5e–3), the mean of the p(j)'s exceeds 1, and p(t) exceeds the alpha helix and beta sheet probabilities for that window, then a turn is predicted. If the first two conditions are met but the probability of a beta sheet p(b) exceeds p(t), then a sheet is predicted instead.
Secondary structure prediction
Secondary structure prediction is a set of techniques in bioinformatics that aim to predict the secondary structures of proteins and nucleic acid sequences based only on knowledge of their primary structure...
of secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
s in protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, originally developed in the 1970s. The method is based on analyses of the relative frequencies of each 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...
in alpha helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
, beta sheet
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
s, and turns
Turn (biochemistry)
A turn is an element of secondary structure in proteins where the polypeptide chain reverses its overall direction.- Definition :According to the most common definition, a turn is a structural motif where the Cα atoms of two residues separated by few peptide bonds are in close approach A turn is...
based on known protein structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
s solved with X-ray crystallography
X-ray crystallography
X-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...
. From these frequencies a set of probability parameters were derived for the appearance of each amino acid in each secondary structure type, and these parameters are used to predict the probability
Probability
Probability is ordinarily used to describe an attitude of mind towards some proposition of whose truth we arenot certain. The proposition of interest is usually of the form "Will a specific event occur?" The attitude of mind is of the form "How certain are we that the event will occur?" The...
that a given sequence of amino acids would form a helix, a beta strand, or a turn in a protein. The method is at most about 50–60% accurate in identifying correct secondary structures, which is significantly less accurate than the modern machine learning
Machine learning
Machine learning, a branch of artificial intelligence, is a scientific discipline concerned with the design and development of algorithms that allow computers to evolve behaviors based on empirical data, such as from sensor data or databases...
–based techniques.
Amino acid propensities
The original Chou–Fasman parameters found some strong tendencies among individual amino acids to prefer one type of secondary structure over others. AlanineAlanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
, glutamate, leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, and methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
were identified as helix formers, while proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
and glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
, due to the unique conformational properties of their peptide bond
Peptide bond
This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
s, commonly end a helix. The original Chou–Fasman parameters were derived from a very small and non-representative sample of protein structures due to the small number of such structures that were known at the time of their original work. These original parameters have since been shown to be unreliable and have been updated from a current dataset, along with modifications to the initial algorithm.
The Chou–Fasman method takes into account only the probability that each individual amino acid will appear in a helix, strand, or turn. Unlike the more complex GOR method
GOR method
The GOR method is an information theory-based method for the prediction of secondary structures in proteins. It was developed in the late 1970s shortly after the simpler Chou-Fasman method...
, it does not reflect the conditional probabilities of an amino acid to form a particular secondary structure given that its neighbors already possess that structure. This lack of cooperativity increases its computational efficiency but decreases its accuracy, since the propensities of individual amino acids are often not strong enough to render a definitive prediction.
Algorithm
The Chou–Fasman method predicts helices and strands in a similar fashion, first searching linearly through the sequence for a "nucleation" region of high helix or strand probability and then extending the region until a subsequent four-residue window carries a probability of less than 1. As originally described, four out of any six contiguous amino acids were sufficient to nucleate helix, and three out of any contiguous five were sufficient for a sheet. The probability thresholds for helix and strand nucleations are constant but not necessarily equal; originally 1.03 was set as the helix cutoff and 1.00 for the strand cutoff.Turns are also evaluated in four-residue windows, but are calculated using a multi-step procedure because many turn regions contain amino acids that could also appear in helix or sheet regions. Four-residue turns also have their own characteristic amino acids; proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
and glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
are both common in turns. A turn is predicted only if the turn probability is greater than the helix or sheet probabilities and a probability value based on the positions of particular amino acids in the turn exceeds a predetermined threshold. The turn probability p(t) is determined as:
where j is the position of the amino acid in the four-residue window. If p(t) exceeds an arbitrary cutoff value (originally 7.5e–3), the mean of the p(j)'s exceeds 1, and p(t) exceeds the alpha helix and beta sheet probabilities for that window, then a turn is predicted. If the first two conditions are met but the probability of a beta sheet p(b) exceeds p(t), then a sheet is predicted instead.