MODELING HEPARIN INDUCED CONFORMATIONAL CHANGES IN INTERLEUKINE-5

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cytokine IL-5 functions to simulate B cell growth increase immunoglobulin secretion and eosinophil activation. It holds a key role in allergic diseases such as asthma and allergic rhinitis where eosinophils cause the maximum tissue damage. Dr. Coombe and her collaborators have characterized the interaction of IL-5 with heparin in detail. Site directed mutagenesis analyses on IL-5 have also been performed. Some initial computational modeling of IL-5 ligand binding has been performed too. We will be using automated docking and molecular dynamics simulations to characterize the interaction of IL-5 with heparin. The goal is to understand any key structural changes that might be brought about in the protein upon ligand binding and how that may affect IL-5 signaling via the IL-5 receptor complex.