Characterization of disordered proteins with ENSEMBLE

UNLABELLED ENSEMBLE is a computational approach for determining a set of conformations that represents the structural ensemble of a disordered protein based on input experimental data. The disordered protein can be an unfolded or intrinsically disordered state. Here, we introduce the latest version of the program, which has been enhanced to facilitate its general release and includes an intuitive user interface, as well as new approaches to treat data and analyse results. AVAILABILITY AND IMPLEMENTATION ENSEMBLE is a program implemented in C and embedded in a Perl wrapper. It is supported on main Linux distributions. Source codes and installation files, including a detailed example, can be freely downloaded at http://abragam.med.utoronto.ca/∼JFKlab.

[1]  C. Hogue,et al.  A fast method to sample real protein conformational space , 2000, Proteins.

[2]  Charles D Schwieters,et al.  The Xplor-NIH NMR molecular structure determination package. , 2003, Journal of magnetic resonance.

[3]  Rolf Boelens,et al.  MINOES: A new approach to select a representative ensemble of structures in NMR studies of (partially) unfolded states. Application to Δ25‐PYP , 2009, Proteins.

[4]  Randy J. Read,et al.  Overview of the CCP4 suite and current developments , 2011, Acta crystallographica. Section D, Biological crystallography.

[5]  J. Marsh,et al.  Structural diversity in free and bound states of intrinsically disordered protein phosphatase 1 regulators. , 2010, Structure.

[6]  D. Svergun,et al.  CRYSOL : a program to evaluate X-ray solution scattering of biological macromolecules from atomic coordinates , 1995 .

[7]  J. Marsh,et al.  Structure and disorder in an unfolded state under nondenaturing conditions from ensemble models consistent with a large number of experimental restraints. , 2009, Journal of molecular biology.

[8]  Julie D. Forman-Kay,et al.  Structural signature of the MYPT1-PP1 interaction. , 2011, Journal of the American Chemical Society.

[9]  Martin Blackledge,et al.  NMR characterization of long-range order in intrinsically disordered proteins. , 2010, Journal of the American Chemical Society.

[10]  J. García de la Torre,et al.  Prediction of hydrodynamic and other solution properties of rigid proteins from atomic- and residue-level models. , 2011, Biophysical journal.

[11]  D. Wishart,et al.  Rapid and accurate calculation of protein 1H, 13C and 15N chemical shifts , 2003, Journal of Biomolecular NMR.

[12]  Collin M. Stultz,et al.  Modeling Intrinsically Disordered Proteins with Bayesian Statistics , 2010, Journal of the American Chemical Society.

[13]  M. Bolognesi,et al.  Function and Structure of Inherently Disordered Proteins This Review Comes from a Themed Issue on Proteins Edited Prediction of Non-folding Proteins and Regions Frequency of Disordered Regions Protein Evolution Partitioning Unstructured Proteins and Regions into Groups Involvement of Inherently Diso , 2022 .

[14]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[15]  J. Forman-Kay,et al.  Calculation of ensembles of structures representing the unfolded state of an SH3 domain. , 2001, Journal of molecular biology.

[16]  C. Dobson,et al.  Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations. , 2005, Journal of the American Chemical Society.

[17]  Joseph A Marsh,et al.  Ensemble modeling of protein disordered states: Experimental restraint contributions and validation , 2011, Proteins.

[18]  Luca Mollica,et al.  Towards a robust description of intrinsic protein disorder using nuclear magnetic resonance spectroscopy. , 2012, Molecular bioSystems.

[19]  Joseph A Marsh,et al.  Improved structural characterizations of the drkN SH3 domain unfolded state suggest a compact ensemble with native-like and non-native structure. , 2007, Journal of molecular biology.

[20]  Christopher J. Oldfield,et al.  Intrinsically disordered proteins in human diseases: introducing the D2 concept. , 2008, Annual review of biophysics.

[21]  Christopher W V Hogue,et al.  Probabilistic sampling of protein conformations: New hope for brute force? , 2002, Proteins.

[22]  H. Dyson,et al.  Intrinsically unstructured proteins and their functions , 2005, Nature Reviews Molecular Cell Biology.

[23]  M. Tyers,et al.  Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase. , 2010, Structure.

[24]  H. Dyson,et al.  Unfolded proteins and protein folding studied by NMR. , 2004, Chemical reviews.