HLA-DP2 binding prediction by molecular dynamics simulations

Irini Doytchinova, Peicho Petkov, Ivan Dimitrov, Mariyana Atanasova, Darren R Flower

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1918-28
Number of pages11
JournalProtein Science
Issue number11
Early online date27 Sept 2011
Publication statusPublished - Nov 2011


  • MHC class II proteins
  • peptide-MHC complex
  • molecular dynamics
  • MHC binding prediction
  • HLA-DP2


Dive into the research topics of 'HLA-DP2 binding prediction by molecular dynamics simulations'. Together they form a unique fingerprint.

Cite this