Cytokines are very important inflammatory signaling molecules that have been intensively studied since their identification in 1957. Crystal structures and recently electron microscopy structures of cytokines in complex with their receptors have been reported but their quaternary structures involving several cytokines and cytokines receptors are not well understood. Professor Saha will use the UWM Discovery and Innovation grant to support his computational approach that applies molecular dynamics simulations to improve our molecular understanding of these complexes.
This computational approach will also allow the Saha Group to find important binding regions of these complexes that when disrupted can result in dissociation. Thus, in another aim of the grant, Prof. Saha will work with the MIDD to identify new small molecules that can disrupt the interactions between IL-13 and IL-4 that bind the heterodimer of IL-4Rα & IL-13 Rα1. Compounds identified by virtual screening will be purchased or synthesized and analyzed by ELISA and isothermal titration calorimetry. The goal of this research is to discover new treatment approaches for atopic dermatitis based on small molecule inhibitors of cytokine signaling.