Journal of Computer-Aided Molecular Design

, Volume 30, Issue 7, pp 569–581 | Cite as

A computational docking study on the pH dependence of peptide binding to HLA-B27 sub-types differentially associated with ankylosing spondylitis

  • Onur Serçinoğlu
  • Gülin Özcan
  • Zeynep Kutlu Kabaş
  • Pemra OzbekEmail author


A single amino acid difference (Asp116His), having a key role in a pathogenesis pathway, distinguishes HLA-B*27:05 and HLA-B*27:09 sub-types as associated and non-associated with ankylosing spondylitis, respectively. In this study, molecular docking simulations were carried out with the aim of comprehending the differences in the binding behavior of both alleles at varying pH conditions. A library of modeled peptides was formed upon single point mutations aiming to address the effect of 20 naturally occurring amino acids at the binding core peptide positions. For both alleles, computational docking was applied using Autodock 4.2. Obtained free energies of binding (FEB) were compared within the peptide library and between the alleles at varying pH conditions. The amino acid preferences of each position were studied enlightening the role of each on binding. The preferred amino acids for each position of pVIPR were found to be harmonious with experimental studies. Our results indicate that, as the pH is lowered, the capacity of HLA-B*27:05 to bind peptides in the library is largely lost. Hydrogen bonding analysis suggests that the interaction between the main anchor positions of pVIPR and their respective binding pocket residues are affected from the pH the most, causing an overall shift in the FEB profiles.


Computational molecular docking Autodock 4.2 HLA docking Peptide docking HLA-B27 pH change Cross-presentation 



This work was supported by TUBITAK under Grant 113M293.

Compliance with ethical standards

Conflict of interest

No conflicting financial interests exist.

Supplementary material

10822_2016_9934_MOESM1_ESM.docx (723 kb)
Supplementary material 1 (DOCX 727 kb)


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Faculty of Engineering, Department of Bioengineering, Goztepe Campus, MC-373Marmara UniversityGoztepe, IstanbulTurkey

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