One of the challenges to understanding large systems biology datasets is the ability to combine the results from orthogonal approaches and integrate targeted functional information into a comprehensive model. In addition, a major obstacle in structural biology is that many protein assemblies resist characterization by traditional approaches such as X-ray crystallography, NMR spectroscopy, or high resolution EM. Integrative structure determination is a valuable approach to overcoming the limitations of individual approaches, by leveraging experimental data from several orthogonal sources. We will leverage data provided by HARC researchers and collaborators, to build structural and network models that provide mechanistic insights into how HIV counteracts restriction pathways and hijacks host cellular pathways. Specifically, we will: provide essential statistical and quantitative analysis of proteomic datasets, apply tools for network, pathway, and functional analysis of multidimensional proteomic datasets, and develop and apply an effective pipeline for integrative structure determination of HIV-human protein complexes.