Conformational states of macromolecular assemblies explored by integrative structure calculation

A detailed description of macromolecular assemblies in multiple conformational states can be very valuable for understanding cellular processes. At present, structural determination of most assemblies in different biologically relevant conformations cannot be achieved by a single technique and thus requires an integrative approach that combines information from multiple sources. Different techniques require different computational methods to allow efficient and accurate data processing and analysis. Here, we summarize the latest advances and future challenges in computational methods that help the interpretation of data from two techniques—mass spectrometry and three-dimensional cryo-electron microscopy (with focus on alignment and classification of heterogeneous subtomograms from cryo-electron tomography). We evaluate how new developments in these two broad fields will lead to further integration with atomic structures to broaden our picture of the dynamic behavior of assemblies in their native environment