PLoS By Category | Recent PLoS Articles

Biophysics - Hematology - Immunology

Predicting HLA Class I Non-Permissive Amino Acid Residues Substitutions
Published: Wednesday, August 08, 2012
Author: T. Andrew Binkowski et al.

by T. Andrew Binkowski, Susana R. Marino, Andrzej Joachimiak

Prediction of peptide binding to human leukocyte antigen (HLA) molecules is essential to a wide range of clinical entities from vaccine design to stem cell transplant compatibility. Here we present a new structure-based methodology that applies robust computational tools to model peptide-HLA (p-HLA) binding interactions. The method leverages the structural conservation observed in p-HLA complexes to significantly reduce the search space and calculate the system’s binding free energy. This approach is benchmarked against existing p-HLA complexes and the prediction performance is measured against a library of experimentally validated peptides. The effect on binding activity across a large set of high-affinity peptides is used to investigate amino acid mismatches reported as high-risk factors in hematopoietic stem cell transplantation.