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Inferential optimization for simultaneous fitting of multiple components into a CryoEM map of their assembly

Lasker, K. and Topf, Maya and Sali, A. and Wolfson, H.J. (2009) Inferential optimization for simultaneous fitting of multiple components into a CryoEM map of their assembly. Journal of Molecular Biology 388 (1), pp. 180-184. ISSN 0022-2836.

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Official URL: http://dx.doi.org/10.1016/j.jmb.2009.02.031

Abstract

Models of macromolecular assemblies are essential for a mechanistic description of cellular processes. Such models are increasingly obtained by fitting atomic-resolution structures of components into a density map of the whole assembly. Yet, current density-fitting techniques are frequently insufficient for an unambiguous determination of the positions and orientations of all components. Here, we describe MultiFit, a method used for simultaneously fitting atomic structures of components into their assembly density map at resolutions as low as 25 Å. The component positions and orientations are optimized with respect to a scoring function that includes the quality-of-fit of components in the map, the protrusion of components from the map envelope, and the shape complementarity between pairs of components. The scoring function is optimized by our exact inference optimizer DOMINO (Discrete Optimization of Multiple INteracting Objects) that efficiently finds the global minimum in a discrete sampling space. MultiFit was benchmarked on seven assemblies of known structure, consisting of up to seven proteins each. The input atomic structures of the components were obtained from the Protein Data Bank, as well as by comparative modeling based on a 16–99% sequence identity to a template structure. A near-native configuration was usually found as the top-scoring model. Therefore, MultiFit can provide initial configurations for further refinement of many multicomponent assembly structures described by electron microscopy.

Item Type: Article
Keyword(s) / Subject(s): Electron microscopy, protein structure modeling, docking, optimization, macromolecular assemblies
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 04 Aug 2010 14:09
Last Modified: 17 Apr 2013 12:17
URI: http://eprints.bbk.ac.uk/id/eprint/1150

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