HLA-DP2 binding prediction by molecular dynamics simulations

Doytchinova, Irini, Petkov, Peicho, Dimitrov, Ivan, Atanasova, Mariyana and Flower, Darren R (2011). HLA-DP2 binding prediction by molecular dynamics simulations. Protein Science, 20 (11), pp. 1918-28.


Major histocompatibility complex (MHC) II proteins bind peptide fragments derived from pathogen antigens and present them at the cell surface for recognition by T cells. MHC proteins are divided into Class I and Class II. Human MHC Class II alleles are grouped into three loci: HLA-DP, HLA-DQ, and HLA-DR. They are involved in many autoimmune diseases. In contrast to HLA-DR and HLA-DQ proteins, the X-ray structure of the HLA-DP2 protein has been solved quite recently. In this study, we have used structure-based molecular dynamics simulation to derive a tool for rapid and accurate virtual screening for the prediction of HLA-DP2-peptide binding. A combinatorial library of 247 peptides was built using the "single amino acid substitution" approach and docked into the HLA-DP2 binding site. The complexes were simulated for 1 ns and the short range interaction energies (Lennard-Jones and Coulumb) were used as binding scores after normalization. The normalized values were collected into quantitative matrices (QMs) and their predictive abilities were validated on a large external test set. The validation shows that the best performing QM consisted of Lennard-Jones energies normalized over all positions for anchor residues only plus cross terms between anchor-residues.

Publication DOI: https://doi.org/10.1002/pro.732
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Additional Information: Copyright © 2011 The Protein Society.
Uncontrolled Keywords: MHC class II proteins,peptide-MHC complex,molecular dynamics,MHC binding prediction,HLA-DP2,Biochemistry,Molecular Biology
Full Text Link: https://www.ncb ... les/PMC3267955/
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://onlineli ... ro.732/abstract (Publisher URL)
Published Date: 2011-11
Authors: Doytchinova, Irini
Petkov, Peicho
Dimitrov, Ivan
Atanasova, Mariyana
Flower, Darren R ( 0000-0002-8542-7067)

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