title: SPI-EM: towards a tool for predicting CATH superfamilies in 3D-EM maps.
abstract: In this paper the theoretical framework used to build a superfamily probability in electron microscopy (SPI-EM) is presented. SPI-EM is a new tool for determining the homologous superfamily to which a protein domain belongs looking at its three-dimensional electron microscopy map. The homologous superfamily is assigned according to the domain-architecture database CATH. Our method follows a probabilistic approach applied to the results of fitting protein domains into maps of proteins and the computation of local cross-correlation coefficient measures. The method has been tested and its usefulness proven with isolated domains at a resolution of 8 A and 12 A. Results obtained with simulated and experimental data at 10 A suggest that it is also feasible to detect the correct superfamily of the domains when dealing with electron microscopy maps containing multi-domain proteins. The inherent difficulties and limitations that multi-domain proteins impose are discussed. Our procedure is complementary to other techniques existing in the field to detect structural elements in electron microscopy maps like alpha-helices and beta-sheets. Based on the proposed methodology, a database of relevant distributions is being built to serve the community.
authors.affiliation: National Center for Biotechnology, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Velázquez-Muriel
authors.forename: Carlos O S
authors.initials: CO
authors.lastname: Sorzano
authors.forename: Sjors H W
authors.initials: SH
authors.lastname: Scheres
authors.forename: José-María
authors.initials: JM
authors.lastname: Carazo
mesh_terms: D003116:Color; D003198:Computer Simulation; D030562:Databases, Protein; D008854:Microscopy, Electron / Q000379:methods*; D008958:Models, Molecular; D011336:Probability; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000145:classification* / Q000648:ultrastructure*; D012984:Software
chemical_list: D011506:Proteins