Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

71-POS Board 24 Comparison of the Binding Behavior of HLA-B Alleles Related to Ankylosing Spondylitis Disease by Computational Methods Gülin Özcan , Onur Serçinoglu, Zeynep Kutlu Kabas, Pemra Özbek. Marmara University, Kadıköy, Turkey. Ankylosing Spondylitis (AS), which is an autoimmune disease affecting the axial skeleton, is associated with B*27 allele of Human Leukocyte Antigen (HLA). The single amino acid replacement (ASP116HIS), having a key role in pathogenesis pathway, distinguishes HLA- B*27:05 and HLA-B*27:09 alleles as non-associated and associated with AS, respectively. Although sharing the same peptide repertoire, both alleles interact with T cells differently. Hence, understanding the differences in binding behavior is of considerable interest both from structural and immunological points of view. In this study, molecular docking and molecular dynamics simulations are carried on aiming to comprehend the differences in the binding behavior of both alleles. Initially, a ‘re-docking’ experiment is applied on both HLA-B*2705 and HLA-B*27:09 alleles by Autodock Vina for the validation of the molecular docking protocol. This validated protocol is then performed on a library of modeled peptides formed upon single point mutations aiming to address the effect of 20 naturally occurring amino acids at the binding core peptide positions. The free binding energies (FBEs) obtained from computational docking experiments are compared within the peptide library and between the alleles. The amino acid preferences of each position are studied enlightening the role of each on binding. Based on the amino acid preferences of each position, 9 individual peptides are constructed by changing a single position while keeping the rest of the peptide fixed. Molecular dynamics simulations are performed on the docked structures for 2 ns aiming to see the effect of the mutations on the root mean square deviation (RMSD) and cross-correlations. As a result of this study, an informative guideline would be obtained for the binding behavior of the HLA-B*27 molecules in a comparative manner.

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