Conformation-independent structural comparison of macromolecules with ProSMART

Journal Article · Mon Sep 01 04:00:00 EDT 2014 · Acta Crystallographica. Section D: Biological Crystallography

DOI:https://doi.org/10.1107/S1399004714016241· OSTI ID:22347751

Fischer, Marcus ^[1]; McNicholas, Stuart ^[2]; Murshudov, Garib N. ^[3]

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1. University of California San Francisco, San Francisco, CA 94158 (United States)
2. University of York, Heslington, York YO10 5DD (United Kingdom)
3. MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom)

The Procrustes Structural Matching Alignment and Restraints Tool (ProSMART) has been developed to allow local comparative structural analyses independent of the global conformations and sequence homology of the compared macromolecules. This allows quick and intuitive visualization of the conservation of backbone and side-chain conformations, providing complementary information to existing methods. 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.

• OSTI ID: 22347751
• Journal Information: Acta Crystallographica. Section D: Biological Crystallography, Journal Name: Acta Crystallographica. Section D: Biological Crystallography Journal Issue: Pt 9 Vol. 70; ISSN ABCRE6; ISSN 0907-4449
• Country of Publication: Denmark
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
ALIGNMENT
CHARGES
CONFORMATIONAL CHANGES
DNA
LIGANDS
MATHEMATICAL SOLUTIONS
PROTEINS
SOLUTIONS