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Title: Continuum secondary structure captures protein flexibility
Authors: Claus A. F. Andersen1,2, Arthur G. Palmer1, Søren Brunak2 & Burkhard Rost1, 3
  1. Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street BB217, New York, NY 10032, USA, Andersen: ca2@cubic.bioc.columbia.edu, Palmer:agp6@columbia.edu, Rost:rost@columbia.edu
  2. Center for Biological Sequence Analysis, BioCentrum, The Technical University of Denmark, DK-2800 Lyngby, Denmark, Andersen: ca2@cbs.dtu.dk, Brunak: brunak@cbs.dtu.dk
  3. Columbia University Center for Computational Biology and Bioinformatics (C2B2), Russ Berrie Pavilion, 1150 St. Nicholas Avenue, New York, NY 10032, USA
Quote: Structure, 2002, 10, 175-185

Abstract for
Continuum secondary structure captures protein flexibility

The DSSP program automates protein secondary structure assignment, using an algorithm that assigns every residue to one of eight states. However, any discrete assignment is incomplete, because the continuum of thermal fluctuations cannot be described. Hence, a continuous assignment of secondary structure that replaces 'static' by 'dynamic' states is proposed. Technically, the continuum results from calculating weighted averages over ten discrete DSSP assignments with different hydrogen bond thresholds. The final set of weights for the continuous assignment maximised the secondary structure similarity between different NMR models of the same protein. Individual NMR models obtained from high-quality data sets were more similar to one another than were X-ray structures of close homologues. More importantly, the final continuous assignment for a single NMR model successfully reflected the structural variations observed between all NMR models in the ensemble. The structural variations between NMR models were verified to correlate with thermal motion by comparison with generalised order parameters for backbone amide moieties. The final continuous DSSP assignments reflected the structural variations due to thermal fluctuations as detected by NMR spectroscopy. The continuous assignment reproduces the structural variation between many NMR models from one single model; therefore, functionally important variation can be extracted from a single X-ray structure using the continuous assignment procedure. Thus, continuous assignments of secondary structure may impact future protein structure analysis, comparison and prediction.

 

Key words: protein secondary structure assignment, evaluation, protein motion, protein structure prediction, protein function, NMR spectroscopy, structure comparison.



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