Abstract:
:Identification of MHC binding peptides is essential for understanding the molecular mechanism of immune response. However, most of the prediction methods use motifs/profiles derived from experimental peptide binding data for specific MHC alleles, thus limiting their applicability only to those alleles for which such data is available. In this work we have developed a structure-based method which does not require experimental peptide binding data for training. Our method models MHC-peptide complexes using crystal structures of 170 MHC-peptide complexes and evaluates the binding energies using two well known residue based statistical pair potentials, namely Betancourt-Thirumalai (BT) and Miyazawa-Jernigan (MJ) matrices. Extensive benchmarking of prediction accuracy on a data set of 1654 epitopes from class I and class II alleles available in the SYFPEITHI database indicate that BT pair-potential can predict more than 60% of the known binders in case of 14 MHC alleles with AUC values for ROC curves ranging from 0.6 to 0.9. Similar benchmarking on 29,522 class I and class II MHC binding peptides with known IC(50) values in the IEDB database showed AUC values higher than 0.6 for 10 class I alleles and 9 class II alleles in predictions involving classification of a peptide to be binder or non-binder. Comparison with recently available benchmarking studies indicated that, the prediction accuracy of our method for many of the class I and class II MHC alleles was comparable to the sequence based methods, even if it does not use any experimental data for training. It is also encouraging to note that the ranks of true binding peptides could further be improved, when high scoring peptides obtained from pair potential were re-ranked using all atom forcefield and MM/PBSA method.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Kumar N,Mohanty Ddoi
10.1039/c0mb00013bsubject
Has Abstractpub_date
2010-12-01 00:00:00pages
2508-20issue
12eissn
1742-206Xissn
1742-2051journal_volume
6pub_type
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