Ranking of binding and nonbinding peptides to MHC class I molecules using inverse folding approach: Implications for vaccine design




Satarudra Prakash Singh1, 2and Bhartendu Nath Mishra 2,*





1Amity Institute of Biotechnology, Amity University Uttar Pradesh, Gomati Nagar, Lucknow-226010, India.2Department of Biotechnology, Institute of Engineering & Technology, U.P. Technical University, Sitapur Road, Lucknow-226001, India.


Email; * Corresponding author


Article Type


Prediction Model




received September 21, 2008, accepted September 30, 2008; published October 24, 2008


T cell recognition of the peptide–MHC complex initiates a cascade of immunological events necessary for immune responses. Accurate T-cell epitope prediction is an important part of the vaccine designing. Development of predictive algorithms based on sequence profile requires a very large number of experimental binding peptide data to major histocompatibility complex (MHC) molecules. Here we used inverse folding approach to study the peptide specificity of MHC Class-I molecule with the aim of obtaining a better differentiation between binding and nonbinding sequence. Overlapping peptides, spanning the entire protein sequence, are threaded through the backbone coordinates of a known peptide fold in the MHC groove, and their interaction energies are evaluated using statistical pairwise contact potentials. We used the Miyazawa & Jernigan and Betancourt & Thirumalai tables for pairwise contact potentials, and two distance criteria (Nearest atom < 4.0 Å & C-beta< 7.0 Å) for ranking the peptides in an ascending order according to their energy values, and in most cases, known antigenic peptides are highly ranked. The predictions from threading improved when used multiple templates and average scoring scheme. In general, when structural information about a protein-peptide complex is available, the current application of the threading approach can be used to screen a large library of peptides for selection of the best binders to the target protein. The proposed scheme may significantly reduce the number of peptides to be tested in wet laboratory for epitope based vaccine design.





epitope; MHC; threading; template; contact potential




Singh et al., Bioinformation 3(1): 72-82 (2008)


Edited by


P. Kangueane








Biomedical Informatics




This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.