On the determinants of residence times and dissociation mechanisms of complexes of interleukin-13 with its low and high affinity receptors

Authors

Herb, N., Brajkovic, M., D'Arrigo, G., Kokh, D. B., Wade, R. C.

Abstract

Interleukin-13 (IL-13) is an immunomodulatory cell signaling cytokine that has been implicated in neurodegenerative disease and chronic inflammation. IL-13 binds to its low and high affinity receptors, IL-13 receptor 1 (IL-13R1) and IL-13 receptor 2 (IL-13R2), respectively, with residence times that vary accordingly. As the binding kinetics of the cytokine-receptor complexes influence cellular responses, we employed the molecular dynamics (MD) simulation-based {tau}-random acceleration molecular dynamics method ({tau}RAMD) to compute relative residence times for wild-type (WT) IL-13 and 19 IL-13 mutants to the two receptors. Comparison with experimental kinetic data shows that the {tau}RAMD computations capture the trends in residence times. Analysis of simulated dissociation trajectories of the cytokine-receptor complexes reveals two distinct dissociation pathways of IL-13 from each of the receptors. This study thus pinpoints key determinants of the interaction of IL-13 with its receptors which could be targeted for therapeutic design.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 19 Aug 2026.

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