title: FOLD-EM: automated fold recognition in medium- and low-resolution (4-15 Å) electron density maps.
abstract: BACKGROUND
  Owing to the size and complexity of large multi-component biological assemblies, the most tractable approach to determining their atomic structure is often to fit high-resolution radiographic or nuclear magnetic resonance structures of isolated components into lower resolution electron density maps of the larger assembly obtained using cryo-electron microscopy (cryo-EM). This hybrid approach to structure determination requires that an atomic resolution structure of each component, or a suitable homolog, is available. 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.
  
  
  RESULTS
  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 Å) electron density maps and return a model of the constituent polypeptides in a fully automated fashion. As a by-product, FOLD-EM can also do flexible multi-domain fitting that may provide insight into conformational changes that occur in macromolecular assemblies.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 7555-0647, USA. mitul@cs.stanford.edu
authors.forename: Mitul
authors.initials: M
authors.lastname: Saha
authors.forename: Marc C
authors.initials: MC
authors.lastname: Morais
mesh_terms: D000465:Algorithms; D018834:Chaperonin 60 / Q000737:chemistry; D020285:Cryoelectron Microscopy; D030562:Databases, Protein; D004583:Electrons; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012984:Software; D040681:Structural Homology, Protein
chemical_list: D018834:Chaperonin 60; D046911:Macromolecular Substances