Use of evolutionary information in the fitting of atomic level protein models in low resolution cryo-EM map of a protein assembly improves the accuracy of the fitting

Joseph, Agnel P and Swapna, Lakshmipuram S and Rakesh, Ramachandran and Srinivasan, Narayanaswamy (2016) Use of evolutionary information in the fitting of atomic level protein models in low resolution cryo-EM map of a protein assembly improves the accuracy of the fitting. In: JOURNAL OF STRUCTURAL BIOLOGY, 195 (3). pp. 294-305.

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Abstract

Protein-protein interface residues, especially those at the core of the interface, exhibit higher conservation than residues in solvent exposed regions. Here, we explore the ability of this differential conservation to evaluate fittings of atomic models in low-resolution cryo-EM maps and select models from the ensemble of solutions that are often proposed by different model fitting techniques. As a prelude, using a non-redundant and high-resolution structural dataset involving 125 permanent and 95 transient complexes, we confirm that core interface residues are conserved significantly better than nearby non-interface residues and this result is used in the cryo-EM map analysis. From the analysis of inter-component interfaces in a set of fitted models associated with low-resolution cryo-EM maps of ribosomes, chaperones and proteasomes we note that a few poorly conserved residues occur at interfaces. Interestingly a few conserved residues are not in the interface, though they are close to the interface. These observations raise the potential requirement of refitting the models in the cryo-EM maps. We show that sampling an ensemble of models and selection of models with high residue conservation at the interface and in good agreement with the density helps in improving the accuracy of the fit. This study indicates that evolutionary information can serve as an additional input to improve and validate fitting of atomic models in cryo-EM density maps. (C) 2016 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Publication:	JOURNAL OF STRUCTURAL BIOLOGY
Additional Information:	Copy right for this article belongs to the ACADEMIC PRESS INC ELSEVIER SCIENCE, 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	22 Oct 2016 05:51
Last Modified:	22 Oct 2016 05:51
URI:	http://eprints.iisc.ac.in/id/eprint/54645

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