Chou Fasman Algorithm

RRA, Division of Biochemistry, DWAH-FLS-

2018
JSSAHER
• Chou & Fasman
• (1974)

RRA, Division of Biochemistry, DWAH-FLS-

2018
JSSAHER
 Protein Structure Prediction

Primary structure No problems

Overall 77% accurate at

Secondary structure predicting

Tertiary structure Overall 30% accurate at

predicting
Quaternary structure No reliable means of
predicting yet

Function Do you feel like guessing?

RRA, Division of Biochemistry, DWAH-FLS-

2018
JSSAHER
 Chou-Fasman Algorithm
• Analyzed the frequency of the 20 amino acids in alpha
helices, Beta sheets and turns.

• Ala (A), Glu (E), Leu (L), and Met (M) are strong predictors
of  helices.

• Pro (P) and Gly (G) break  helices.

• When 4 of 5 amino acids have a high probability of being in

an alpha helix, it predicts a alpha helix.

• When 3 of 5 amino acids have a high probability of being in

a  strand, it predicts a  strand.

• 20184 amino acids are RRA,

used Divisionto predict
of Biochemistry,
JSSAHER
turns.
DWAH-FLS-
 Method
• Assigning a set of prediction values to a
residue, based on statistic analysis of 15
proteins.

• Applying a simple algorithm to those numbers.

• Propensity : an inclination or natural tendency

to behave in a particular way.
RRA, Division of Biochemistry, DWAH-FLS-
2018
JSSAHER
 Calculation of Propensities
Pr[i/-sheet]/Pr[i]
Pr[i/-helix]/Pr[i]
Pr[i/other]/Pr[i]
• Determine the probability that amino acid i is in each
structure, normalized by the background probability that i
occurs at all.

Example:
Lets say that there are 20,000 amino acids in the database, of
which 2000 are serine, and there are 5000 amino acids in helical
conformation, of which 500 are serine.
Then the helical propensity for serine is: (500/5000) / (2000/20000) =
1.0

RRA, Division of Biochemistry, DWAH-FLS-

2018
JSSAHER
 Calculation of preference parameters

• Preference parameter > 1.0

 specific residue has a preference for the
specific secondary structure.
• Preference parameter = 1.0
 specific residue does not have a preference
for, nor dislikes the specific secondary
structure.
• Preference parameter < 1.0
 specific residue dislikes the specific
secondary structure.
RRA, Division of Biochemistry, DWAH-FLS-
2018
JSSAHER
Name P(a) P(b) P(turn) f(i) f(i+1) f(i+2) f(i+3)

Alanine 1.42 0.83 0.66 0.06 0.076 0.035 0.058

RRA, Division of Biochemistry, DWAH-FLS-

2018
JSSAHER
Residue P(a) P(b) P(t) f(i) f(i+1) f(i+2) f(i+3)

Ala 1.45 0.97 0.57 0.049 0.049 0.034 0.029

Arg 0.79 0.90 1.00 0.051 0.127 0.025 0.101

Asn 0.73 0.65 1.68 0.101 0.086 0.216 0.065

Asp 0.98 0.80 1.26 0.137 0.088 0.069 0.059

Cys 0.77 1.30 1.17 0.089 0.022 0.111 0.089

Gln 1.17 1.23 0.56 0.050 0.089 0.030 0.089

Glu 1.53 0.26 0.44 0.011 0.032 0.053 0.021

Gly 0.53 0.81 1.68 0.104 0.090 0.158 0.113

His 1.24 0.71 0.69 0.083 0.050 0.033 0.033

Ile 1.00 1.60 0.58 0.068 0.034 0.017 0.051

Leu 1.34 1.22 0.53 0.038 0.019 0.032 0.051

Lys 1.07 0.74 1.01 0.060 0.080 0.067 0.073

Met 1.20 1.67 0.67 0.070 0.070 0.036 0.070

Phe 1.12 1.28 0.71 0.031 0.047 0.063 0.063

Pro 0.59 0.62 1.54 0.074 0.272 0.012 0.062

Ser 0.79 0.72 1.56 0.100 0.095 0.095 0.104

Thr 0.82 1.20 1.00 0.062 0.093 0.056 0.068

Trp 1.14 1.19 1.11 0.045 0.000 0.045 0.205

Tyr 0.61 1.29 1.25 0.136 0.025 0.110 0.102

RRA, Division of Biochemistry, DWAH-FLS-
2018
Val 1.14 1.65 0.30 0.023
JSSAHER 0.029 0.011 0.029
 Successful method?
15 proteins evaluated:
• helix = 46%, ß-sheet = 35%, turn = 65%
• Overall accuracy of predicting the three
conformational states for all residues, helix, b,
and coil, is 56%
Chou & Fasman: Not so great ?
After 1974:improvement of preference
parameters
Garnier-Osguthorpe-Robson (GOR) method
– Neural network models
2018
– Nearest-neighbor method
RRA, Division of Biochemistry, DWAH-FLS-
JSSAHER