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Iosif Vaisman
Introduction to Bioinformatics
Secondary Structure:
Computational Problems
Secondary structure characterization
Secondary structure assignment
Secondary structure prediction
Protein structure classification
Secondary Structure:
Computational Problems
Secondary structure characterization
Secondary structure assignment
Secondary structure prediction
Protein structure classification
Protein Structure Hierarchy
•Primary - the sequence of amino acid residues
•Secondary - ordered regions of primary sequence
(helices, beta-sheets, turns)
•Tertiary - the three-dimensional fold of a protein subunit
•Quaternary - the arrangement of subunits in oligomers.
Adopted from Branden and Tooze
Secondary Structure Conformations
Secondary Structure Conformations
alpha helix -57 -
alpha-L 57 47
3-10 helix -49 -
π helix -57 -
type II helix -79 150
β-sheet parallel -119 113
β-sheet antiparallel -139 135
Secondary Structure Assignment
Secondary Structure Assignment Secondary Structure Assignment
.-- sequential resnumber, including chain breaks as extra residues | .-- original PDB resname, not nec. sequential, may contain letters | | .-- amino acid sequence in one letter code | | | .-- secondary structure summary based on columns 19- | | | | xxxxxxxxxxxxxxxxxxxx recommend columns for secstruc details | | | | .-- 3-turns/helix | | | | |.-- 4-turns/helix | | | | ||.-- 5-turns/helix | | | | |||.-- geometrical bend | | | | ||||.-- chirality | | | | |||||.-- beta bridge label | | | | ||||||.-- beta bridge label | | | | ||||||| .-- beta bridge partner resnum | | | | ||||||| | .-- beta bridge partner resnum | | | | ||||||| | |.-- beta sheet label | | | | ||||||| | || .-- solvent accessibility | | | | ||||||| | || |
RESIDUE AA STRUCTURE BP1 BP2 ACC
| | | | ||||||| | || | 35 47 I E + 0 0 2 36 48 R E > S- K 0 39C 97 37 49 Q T 3 S+ 0 0 86 (example from 1EST) 38 50 N T 3 S+ 0 0 34 39 51 W E < -KL 36 98C 6
Secondary Structure:
Computational Problems
Secondary structure characterization
Secondary structure assignment
Secondary structure prediction
Protein structure classification
Secondary Structure Prediction
Methods:
- statistical
- stereochemical
Three-state model: helix, strand, coil
Given a protein sequence:
- NWVLSTAADMQGVVTDGMASGLDKD...
Predict a secondary structure sequence:
- LLEEEELLLLHHHHHHHHHHLHHHL...
Accuracy: 50-85%
Neural Networks Methods
Helix Sheet
MKFGNFLLTYQP [ PELSQTE ] VMKRLVNLGKASEGC...
Input layer
(7x21 units)
Hidden layer
(2 units)
Output layer
(2 units)
Stereochemical Methods
Patterns of hydrophobic and hydrophilic residues
in secondary structure elements:
- segregation of hydrophobic and hydrophilic residues
- hydrophobic residues in the positions 1-2-5 and 1-4-
- oppositely charged polar residues in the positions
1-5 and 1-4 (e.g. Glu (i), Lys (i+4))
Definitions of hydrophobic and hydrophilic
residues (hydrophobicity scales) are ambiguous
Stereochemical Methods
i, i+3 - + + -
i, i+2 + - - +
i, i+1 - + + -
i, i+5 - + + -
i, i+4 + - - +
i, i+3 + - - +
i, i+2 - + + -
F-F F-L L-F L-L
Hydropathic correlations in helices and sheets
Accuracy of prediction
EVA (http://cubic.bioc.columbia.edu/eva/)
Accuracy of Prediction
Q 3 =
PH + PE +PC
N
W = log FP x FN
TP x TN
Range: 50-85%
