Metal-organic frameworks (MOFs) are crystalline nanoporous materials with a variety of potential applications in gas separations and storage. Because thousands of distinct MOFs are known, approaches that can rapidly identify structures with particular promise for specific applications have considerable value. We will describe a hierarchical modeling approach to screen MOFs for membrane-based gas separations, an application that is challenging because it requires information on both adsorption affinity and molecular diffusivities. Our approach uses geometric characterization to screen hundreds of materials, then molecular modeling and quantum chemistry calculations to make detailed predictions about strong candidate materials. We will show examples of using this approach to develop materials for efficient separation of methane and carbon dioxide. We will also describe our progress in fabricating and