epitope prediction and its algorithms
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Epitope prediction and its algorithmsTRANSCRIPT
S.Prasanth Kumar, S.Prasanth Kumar, BioinformaticianBioinformatician
Immunoinformatics
Epitope Prediction and its AlgorithmsEpitope Prediction and its Algorithms
S.Prasanth Kumar, S.Prasanth Kumar, BioinformaticianBioinformatician
S.Prasanth Kumar Dept. of Bioinformatics Applied Botany Centre (ABC) Gujarat University, Ahmedabad, INDIA
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Epitope
Antigenic determinants or Epitopes are the portions of the antigen molecules which are responsible for specificity of the antigens in antigen-antibody (Ag-Ab) reactions and that combine with the antigen binding site of Ab, to which they are complementary.
Antibody Epitope
They occur on the surface of the protein and are more flexible than
the rest of the protein
They have high degree of exposure to the solvent.
The amino acids making the epitope are usually charged and
hydrophilic
Epitope’s Properties and its Types
Sequential / Continuous Epitopes
Antibody Recognized by TH cellsLinear peptide fragmentsAmphipathic helical 9-12 mer
Conformational / Discontinuous Epitopes
Antibody Recognized by both TH & B cellsNon-linear discrete amino acid sequences, come together due to foldingExposed 15-22 mer
Paratope
Paratope
Sites of Antigen binding on Antibody molecule
Immunological Processes
Ag-Ab Complex
MHC molecules function as antigen-recognition molecules
Class I – Presents Ag so that TC
cells recognize & kill. Requires CD8+ on Tc
Class II – Presents Ag so that TH cells recognize & kill. Requires CD4+ on TH
Immunological Processes
Endogenous pathway (class I MHC)
Endogenous antigen Cytosol
Proteasome
Antigenic peptides
peptidases
N-terminally trimmed peptides
TAP (transporter associated with antigen processing)
Immunological Processes
CytosolER
*aminopeptidase associated with antigen processing (ERAAP)
ERAAP
N-terminally trimmed peptides MHC Class I
GC
Exogenous Antigen
Class II
Exogenous pathway (class II MHC) Cell Surface
Immunological Processes
Cytosol
Cell Surface
Where MHC are expressed ? Class-I all nucleated cells e.g. virus infected cells Class-II APCs (macrophages, B lymphocytes, and dendritic cells)
TH cells expresses CD4,CD4 recognizes MHC class II molecules TC cells expresses CD8,CD8 recognizes MHC class I molecules
TH Cell
TCR
CD4
MHC Class II
Antigenic PeptideTC Cell
CD8
MHC Class I
Immuological Responses
B-Cell Epitope Prediction
Hopp & Woods method
……-Ser-Thr-Cys-Asn-Glu-…… ……-Ser-Thr-Val-Asn-Glu-…..
e.g. ser-1, thr-2, cys-3,asn-4,glu-5, etc,…..x-10 alignment score = 22
Based on alignment score predict Antigenicity
1 + 2 + 10 + 4 + 5 = 22
Database of Known Epitopes
% of Epitope aa : % of aa in the avg. composition of a protein
Assigns an antigenicity value for each amino acid from the relative occurrence of the amino acid in epitope
Welling’s method
B-Cell Epitope Prediction
High antigencity value
Extend to 11-13 aa Report Probable
Low antigencity value
Karplus & Schultz
Structural parameters
Parker & Hodges method
B-Cell Epitope Prediction
HPLC from retention co-efficient of model synthetic peptides
Hydrophilicity
Janin’s scale
Summing the ASA parameters for each residue of a seven-residue segment and assigning the sum to the fourth residue
Surface profile Flexibility
Predict Antigenicity
B-Cell Epitope Prediction
Semi-empirical method
Kolaskar & Tongaonkar’s method
Frequencies of occurrence of amino acids in experimentally known epitopes
Physiological properties of amino acid residues
Data of 169 epitopes from 34 different proteins was collected of which 156 which have less than 20 aa per determinant
It is available as Antigen under ExPaSy and in EMBOSS Suite
Predict Validate
T-Cell Epitope Prediction
Margalit, Spouge et al. method
Considers Amphipathic helix segments (tetramer & pentamer motifs)
A polar residueCharged residues &/ Glycine Hydrophobic residues
1st amino acid 2nd amino acid 3rd amino acid&/
4th amino acid
Predict Antigenicity
Rothbard & Taylor method
T-Cell Epitope Prediction
Immunodominant secondary structure capable of binding to MHC with high affinity
Database of Sequence motifs
3D Structures
Sequence based search Predict Antigenicity
Stille et al. method
T-Cell Epitope Prediction
Known MHC polymorphisms from HLA
Identify anchor residues for different polymorphisms
Construct Virtual matrices
…….
……
.
MHC polymorphism
anch
or r
esid
ues
Sequence based search with MHC polymorphism
Predict Antigenicity
T-Cell Epitope Prediction
MHC binding is based on molecular dynamic simulation
Darren R Flower et al. method
Calculate the free energy of binding for a given molecular system
No reliance on known binding data, but based on de novo prediction
Required Experimentally determined structure, or a homology model, of a MHC peptide complex
Databases & Prediction Servers
SYFPEITHIMHCPEPJenPepFIMMMHCBN HLALigand/Motif databaseHIV Molecular Immunology databaseEPIMHC
Prediction of MHC binding
BIMASSYFPEITHI
PREDEPPEpipredict
PredictPropred
MHCPredNetMHC
MHC-binding peptides databases
SYFPEITHI Epitope Prediction Server
SYFPEITHI Epitope Prediction Server
Thank You For Your Attention !!!