  IL-3 is a hemopoietic growth factor that usually targets blood cell
precursors; IL-3R is a cytokine receptor that binds to IL-3. However, IL-3
takes on a different role in the context of glial cells in the nervous system,
where studies show that the protein IL-3 protects against Alzheimer's disease
by activating microglia at their IL-3R receptors, causing the microglia to
clear out the tangles caused by the build-up of misfolded Tau proteins. In this
study, we seek to ascertain what role the secondary structure of IL-3 plays in
its binding with the receptor. The motivation behind this study is to learn
more about the mechanism and identify possible drugs that might be able to
activate it, in hopes of inhibiting the spread of Alzheimer's Disease. From a
preliminary analysis of complexes containing IL-3 and IL-3R, we hypothesized
that the binding is largely due to the interactions of three alpha helix
structures stretching towards the active site on the receptor. The original
Il-3 protein serves as the control in this experiment; the other proteins being
tested are generated through several types of computational de novo protein
design, where machine learning allows for the production of entirely novel
structures. The efficacy of the generated proteins is assessed through docking
simulations with the IL-3R receptor, and the binding poses are also
qualitatively examined to gain insight into the function of the binding. From
the docking data and poses, the most successful proteins were those with
similar secondary structure to IL-3.
