SPI-EM: Towards a Tool For Predicting CATH Superfamilies in 3D-EM Maps

• Published in: Journal of molecular biology 2005-01, Vol.345 (4), p.759-771
• Main Authors: Velázquez-Muriel, Javier A., Sorzano, Carlos O.S., Scheres, Sjors H.W., Carazo, José-María
• Format: Article
• Language: English
• Subjects: Color; Computer Simulation; cross-correlation; Databases, Protein; fitting; fold recognition; Microscopy, Electron - methods; Models, Molecular; Probability; Protein Structure, Tertiary; Proteins - chemistry; Proteins - classification; Proteins - ultrastructure; Software; structural biology; three-dimensional electron microscopy
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2004.11.005

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 Å and 12 Å. Results obtained with simulated and experimental data at 10 Å 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 α-helices and β-sheets. Based on the proposed methodology, a database of relevant distributions is being built to serve the community.