Currently, the most tractable approach to identify the atomic structure of large multi-component biological assemblies is to fit radiographic or nuclear magnetic resonance structures (high-resolution) into electron density maps of cryo-electron microscopy (low-resolution).
The research at UTMB revealed:
“If neither is available, then the amount of structural information regarding that component is limited by the resolution of the cryo-EM map. However, even if a suitable homolog cannot be identified using sequence analysis, a search for structural homologs should still be performed because structural homology often persists throughout evolution even when sequence homology is undetectable, As macromolecules can often be described as a collection of independently folded domains, one way of searching for structural homologs would be to systematically fit representative domain structures from a protein domain database into the medium/low resolution cryo-EM map and return the best fits. Taken together, the best fitting non-overlapping structures would constitute a ‘mosaic’ backbone model of the assembly that could aid map interpretation and illuminate biological function. Using the computational principles of the Scale-Invariant Feature Transform (SIFT), we have developed FOLD-EM-a computational tool that can identify folded macromolecular domains in medium to low resolution (4-15 A) electron density maps and return a model of the constituent polypeptides in a fully automated fashion.”
FOLD-EM uses a computational principle of the Scale-Invariant Feature Transform (SIFT). It produces electron density maps in medium to low resolution (4–15 Å) and return a model of the constituent polypeptides in a fully automated fashion. FOLD-EM also can operate flexible multi-domain fitting that may provide insight into conformational changes occurring in macromolecular assemblies.
The study was published in Oxford Journals, categorized in Bioinfomatics, with the title “FOLD-EM: automated fold recognition in medium- and low-resolution (4-15 A) electron density maps”
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