Journal Article Docking analysis and the possibility of prediction efficacy for an anti-IL-13 biopharmaceutical treatment with tralokinumab and lebrikizumab for bronchial asthma

Nakamura, Yutaka  ,  Sugano, Aki  ,  Ohta, Mika  ,  Takaoka, Yutaka

12 ( 11 )  , p.e0188407 , 2017-11-20 , Public Library Science
Interleukin-13 (IL-13) is associated with allergic airway inflammation and airway remodeling. Our group found a variant with a single nucleotide polymorphism in the IL13 gene at position + 2044G>A (rs20541) that was expected to result in the non-conservative replacement of a positively charged arginine (R) with a neutral glutamine (Q) at position 144. IL-13Q144 was associated with augmented allergic airway inflammation and bronchial asthma remodeling. There is some indication that anti-IL-13 monoclonal antibodies can demonstrate a positive effect on the clinical course of refractory asthmatic patients. To date, the binding stability of these agents for IL-13Q144 is unknown. The objective of this study was to investigate the prediction efficacy of the anti-IL-13 monoclonal antibodies tralokinumab and lebrikizumab in asthmatic patients with IL-13R144 and IL-13Q144. The three-dimensional (3-D) structure of tralokinumab was obtained from the Protein Data Bank (PDB ID: 5L6Y), and the complete 3-D structure of lebrikizumab was built through homology modeling. For the binding stability analysis, we performed and analyzed docking simulations of IL-13 with tralokinumab or lebrikizumab. The tralokinumab and lebrikizumab structures changed after binding to IL-13 to facilitate binding with IL-13Q144. The stability analysis with tralokinumab and lebrikizumab demonstrated that IL-13Q144 was more stable than IL-13R144 for both the Rosetta energy score and for the free energy of binding. IL-13Q144 might be a promising predictor of responsiveness to tralokinumab and lebrikizumab treatment for bronchial asthma.

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