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Acta Crystallogr D Biol Crystallogr. 2014 Sep;70(Pt 9):2487-99. doi: 10.1107/S1399004714016241. Epub 2014 Aug 29.

Conformation-independent structural comparison of macromolecules with ProSMART.

Author information

1
Structural Studies Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, England.
2
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA.
3
Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5DD, England.

Abstract

The identification and exploration of (dis)similarities between macromolecular structures can help to gain biological insight, for instance when visualizing or quantifying the response of a protein to ligand binding. Obtaining a residue alignment between compared structures is often a prerequisite for such comparative analysis. If the conformational change of the protein is dramatic, conventional alignment methods may struggle to provide an intuitive solution for straightforward analysis. To make such analyses more accessible, the Procrustes Structural Matching Alignment and Restraints Tool (ProSMART) has been developed, which achieves a conformation-independent structural alignment, as well as providing such additional functionalities as the generation of restraints for use in the refinement of macromolecular models. Sensible comparison of protein (or DNA/RNA) structures in the presence of conformational changes is achieved by enforcing neither chain nor domain rigidity. The visualization of results is facilitated by popular molecular-graphics software such as CCP4mg and PyMOL, providing intuitive feedback regarding structural conservation and subtle dissimilarities between close homologues that can otherwise be hard to identify. Automatically generated colour schemes corresponding to various residue-based scores are provided, which allow the assessment of the conservation of backbone and side-chain conformations relative to the local coordinate frame. Structural comparison tools such as ProSMART can help to break the complexity that accompanies the constantly growing pool of structural data into a more readily accessible form, potentially offering biological insight or influencing subsequent experiments.

KEYWORDS:

ProSMART; Procrustes; alignment; external restraints; refinement; structural comparison

PMID:
25195761
PMCID:
PMC4157452
DOI:
10.1107/S1399004714016241
[Indexed for MEDLINE]
Free PMC Article

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