TY - JOUR
T1 - Flexible Fitting in 3D-EM Guided by the Structural Variability of Protein Superfamilies
AU - Velazquez-Muriel, Javier Ángel
AU - Valle, Mikel
AU - Santamaría-Pang, Alberto
AU - Kakadiaris, Ioannis A.
AU - Carazo, José María
N1 - Funding Information:
The authors acknowledge fruitful interactions and discussions with Drs. W. Wriggers, N. Volkmann, W. Chiu, M.L. Baker, and W. Jiang. They also acknowledge the two anonymous reviewers for their valuable comments that indeed helped to improve the quality of the original version of the text. Partial support is acknowledged from the “Comisión Interministerial de Ciencia y Tecnología” of Spain through project BFU2004-00217, the “Fondo de Investigaciones Sanitarias” through project FIS-IM3, the “BBVA” through project 2004X578, the European Union 3D-EM Network of Excellence through project FP6-502828, and the National Institutes of Health through grant 1R01HL67465-01. The authors state that there is no financial conflict of interest that might be construed to influence the result or interpretation of this manuscript.
PY - 2006/7
Y1 - 2006/7
N2 - A method for flexible fitting of molecular models into three-dimensional electron microscopy (3D-EM) reconstructions at a resolution range of 8-12 Å is proposed. The approach uses the evolutionarily related structural variability existing among the protein domains of a given superfamily, according to structural databases such as CATH. A structural alignment of domains belonging to the superfamily, followed by a principal components analysis, is performed, and the first three principal components of the decomposition are explored. Using rigid body transformations for the secondary structure elements (SSEs) plus the cyclic coordinate descent algorithm to close the loops, stereochemically correct models are built for the structure to fit. All of the models are fitted into the 3D-EM map, and the best one is selected based on crosscorrelation measures. This work applies the method to both simulated and experimental data and shows that the flexible fitting was able to produce better results than rigid body fitting.
AB - A method for flexible fitting of molecular models into three-dimensional electron microscopy (3D-EM) reconstructions at a resolution range of 8-12 Å is proposed. The approach uses the evolutionarily related structural variability existing among the protein domains of a given superfamily, according to structural databases such as CATH. A structural alignment of domains belonging to the superfamily, followed by a principal components analysis, is performed, and the first three principal components of the decomposition are explored. Using rigid body transformations for the secondary structure elements (SSEs) plus the cyclic coordinate descent algorithm to close the loops, stereochemically correct models are built for the structure to fit. All of the models are fitted into the 3D-EM map, and the best one is selected based on crosscorrelation measures. This work applies the method to both simulated and experimental data and shows that the flexible fitting was able to produce better results than rigid body fitting.
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U2 - 10.1016/j.str.2006.05.013
DO - 10.1016/j.str.2006.05.013
M3 - Article
C2 - 16843893
AN - SCOPUS:33745813129
SN - 0969-2126
VL - 14
SP - 1115
EP - 1126
JO - Structure
JF - Structure
IS - 7
ER -