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X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy enable us to determine atomic structures of single proteins or other small systems. Larger biomolecular machines were depicted at a relatively coarser granularity. Nowadays, researchers are trying to map systems composed of hundreds of biomacromolecules and describe the dynamics of these systems as they assemble, disassemble, operate, and undergo regulation through interactions with other such systems. Conventional structure determination approaches may be insufficient, thus methods of structural biology need to be integrated. In integrative approaches, information from multiple sources is combined simultaneously to form a common view of a system.
Figure 1. Complex structure solutions
Creative Biostructure provides a first-class structural biology platform and extensive expertise for scientists from academic institutions and the pharmaceutical industry, making the integration of structural information faster. We support mainstream structural determination techniques (such as X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy) as well as newer structural biology techniques. We are attempting to combine these structural biological techniques with cellular biological approaches such as various microscopy imaging, single-molecule techniques, and intracellular NMR. By integrating multiple technologies spanning different resolution scales, it is possible to access structural data that is dynamic at the cellular level. This structural information will facilitate us to understand how proteins or protein complexes interact dynamically with their functional environment based on detailed atomic structure.
In this method, a low-resolution structure is determined by cryo-EM, which is utilized as the initial searching model for X-ray crystallography or NMR spectroscopy. After phasing the high-resolution X-ray data with low-resolution cryo-EM reconstruction by molecular replacement, theoretical phases can be calculated. This method has been shown to be successful in determining the structures of several large complexes, such as ribosomes and viruses.
The combination of multiple technologies such as X-ray crystallography, cryo-EM and NMR spectroscopy allows researchers better study scientific questions by processing comprehensive analyses of the dynamic macromolecular machineries in various organisms.
The combination of mass spectrometry with cryo-EM and/or integrative modeling is particularly promising for studying the topology and structure of large biomolecular machines. Targets studied to date include ribosomes, proteasomes, chromatin remodelers, polymerases, and photosystem complexes.
If you are interested in our integrative structural biology services, please feel free to contact us for more information or a detailed quote.