The authors state no conflict of interest.
Determining macromolecular assembly structures by molecular docking and fitting into an electron density map†
Article first published online: 8 SEP 2010
Copyright © 2010 Wiley-Liss, Inc.
Proteins: Structure, Function, and Bioinformatics
Special Issue: Fourth Meeting on the Critical Assessment of PRedicted Interactions
Volume 78, Issue 15, pages 3205–3211, 15 November 2010
How to Cite
Lasker, K., Sali, A. and Wolfson, H. J. (2010), Determining macromolecular assembly structures by molecular docking and fitting into an electron density map. Proteins, 78: 3205–3211. doi: 10.1002/prot.22845
- Issue published online: 6 OCT 2010
- Article first published online: 8 SEP 2010
- Accepted manuscript online: 17 AUG 2010 12:00AM EST
- Manuscript Accepted: 13 JUL 2010
- Manuscript Revised: 5 JUL 2010
- Manuscript Received: 2 JUN 2010
- National Institutes of Health. Grant Numbers: R01 GM54762, U54 RR022220, PN2 EY016525, R01 GM083960
- Israel Science Foundation. Grant Number: 1403/09
- Sandler Family Supporting Foundation
- Hermann Minkowski Minerva Center for Geometry
- integrative modeling;
- electron microscopy;
- Gaussian mixture model;
- point alignment;
Structural models of macromolecular assemblies are instrumental for gaining a mechanistic understanding of cellular processes. Determining these structures is a major challenge for experimental techniques, such as X-ray crystallography, NMR spectroscopy and electron microscopy (EM). Thus, computational modeling techniques, including molecular docking, are required. The development of most molecular docking methods has so far been focused on modeling of binary complexes. We have recently introduced the MultiFit method for modeling the structure of a multisubunit complex by simultaneously optimizing the fit of the model into an EM density map of the entire complex and the shape complementarity between interacting subunits. Here, we report algorithmic advances of the MultiFit method that result in an efficient and accurate assembly of the input subunits into their density map. The successful predictions and the increasing number of complexes being characterized by EM suggests that the CAPRI challenge could be extended to include docking-based modeling of macromolecular assemblies guided by EM. Proteins 2010. © 2010 Wiley-Liss, Inc.