The Computational Systems Pharmacology Core (Core E) will support the activities of the CMCR with the help of computational pharmacology and systems modeling tools applied to the cellular systems and molecular targets that are being investigated by the four Projects. The specific aims of the Core are the following : (1) Constructing and analyzing computational models for quantitative assessment of the time evolution of the protein-protein interactions that underlie radiation-induced apoptosis, necroptosis, and inflammatory responses; (2) Predicting and optimizing small molecules that can serve as radiomitigators, including repurposable drugs, for selected targets, using a combination of machine learning and chemoinformatics approaches; and (3) Designing polypharmacological strategies and/or combination therapies and identifying the optimal timings for effective intervention protocols. We will also continue to utilize advantageously the methods and software that have been developed and used in the previous funding term, including in particular our server for estimating repurposable drugs and side effects. The Core will take advantage of the computational resources at the Department of Computational & Systems Biology at the University of Pittsburgh, School of Medicine to provide an integrative framework that will help build or prioritize new strategies, and assist in accelerating the research activities of the four Projects.