Insights into protein flexibility: The relationship between normal modes and conformational change upon protein-protein docking

Understanding protein interactions has broad implications for the mechanism of recognition, protein design, and assigning putative functions to uncharacterized proteins. Studying protein flexibility is a key component in the challenge of describing protein interactions. In this work, we characterize...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-07, Vol.105 (30), p.10390-10395
Main Authors: Dobbins, Sara E, Lesk, Victor I, Sternberg, Michael J.E
Format: Article
Language:English
Subjects:
Atoms
Binding sites
Biochemistry
Biological Sciences
Collectivities
Computational Biology - methods
Contrapuntal motion
Coordinate systems
Databases, Protein
Datasets
Enzymes
Escherichia coli - metabolism
Escherichia coli Proteins - chemistry
Magnetic Resonance Spectroscopy
Modeling
Models, Molecular
Models, Statistical
Molecular Conformation
Oscillometry - methods
Periplasmic Proteins - chemistry
Pliability
Protein Binding
Protein Conformation
Protein folding
Protein Interaction Mapping
Proteins
Proteins - chemistry
Statistical mode
Studies
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Summary:Understanding protein interactions has broad implications for the mechanism of recognition, protein design, and assigning putative functions to uncharacterized proteins. Studying protein flexibility is a key component in the challenge of describing protein interactions. In this work, we characterize the observed conformational change for a set of 20 proteins that undergo large conformational change upon association (>2 Å Cα RMSD) and ask what features of the motion are successfully reproduced by the normal modes of the system. We demonstrate that normal modes can be used to identify mobile regions and, in some proteins, to reproduce the direction of conformational change. In 35% of the proteins studied, a single low-frequency normal mode was found that describes well the direction of the observed conformational change. Finally, we find that for a set of 134 proteins from a docking benchmark that the characteristic frequencies of normal modes can be used to predict reliably the extent of observed conformational change. We discuss the implications of the results for the mechanics of protein recognition.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0802496105