From protein sequence to dynamics and disorder with DynaMine

Protein function and dynamics are closely related; however, accurate dynamics information is difficult to obtain. Here based on a carefully assembled data set derived from experimental data for proteins in solution, we quantify backbone dynamics properties on the amino-acid level and develop DynaMine--a fast, high-quality predictor of protein backbone dynamics. DynaMine uses only protein sequence information as input and shows great potential in distinguishing regions of different structural organization, such as folded domains, disordered linkers, molten globules and pre-structured binding motifs of different sizes. It also identifies disordered regions within proteins with an accuracy comparable to the most sophisticated existing predictors, without depending on prior disorder knowledge or three-dimensional structural information. DynaMine provides molecular biologists with an important new method that grasps the dynamical characteristics of any protein of interest, as we show here for human p53 and E1A from human adenovirus 5.

[1]  Christopher J. Oldfield,et al.  Intrinsically disordered protein. , 2001, Journal of molecular graphics & modelling.

[2]  Dmitrij Frishman,et al.  STRIDE: a web server for secondary structure assignment from known atomic coordinates of proteins , 2004, Nucleic Acids Res..

[3]  H Jane Dyson,et al.  Expanding the proteome: disordered and alternatively folded proteins , 2011, Quarterly Reviews of Biophysics.

[4]  Vladimir N Uversky,et al.  Intrinsic disorder in proteins associated with neurodegenerative diseases. , 2009, Frontiers in bioscience.

[5]  Hongwei Wu,et al.  Disorder Predictors Also Predict Backbone Dynamics for a Family of Disordered Proteins , 2011, PloS one.

[6]  Jianlin Cheng,et al.  A comprehensive overview of computational protein disorder prediction methods. , 2012, Molecular bioSystems.

[7]  David S. Wishart,et al.  Application of the random coil index to studying protein flexibility , 2008, Journal of biomolecular NMR.

[8]  Zheng Rong Yang,et al.  RONN: the bio-basis function neural network technique applied to the detection of natively disordered regions in proteins , 2005, Bioinform..

[9]  Niall J. Haslam,et al.  Understanding eukaryotic linear motifs and their role in cell signaling and regulation. , 2008, Frontiers in bioscience : a journal and virtual library.

[10]  Oliver F. Lange,et al.  Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution , 2008, Science.

[11]  Richard J. Edwards,et al.  SLiMDisc: short, linear motif discovery, correcting for common evolutionary descent , 2006, Nucleic acids research.

[12]  Vladimir N Uversky,et al.  A Protein-Chameleon: Conformational Plasticity of α-Synuclein, a Disordered Protein Involved in Neurodegenerative Disorders , 2003, Journal of biomolecular structure & dynamics.

[13]  Sanguthevar Rajasekaran,et al.  Minimotif miner 2nd release: a database and web system for motif search , 2008, Nucleic Acids Res..

[14]  Wayne Boucher,et al.  The CCPN data model for NMR spectroscopy: Development of a software pipeline , 2005, Proteins.

[15]  V. Uversky,et al.  Solution structure and dynamics of the chimeric SH3 domains, SHH- and SHA-"Bergeracs". , 2009, Biochimica et biophysica acta.

[16]  Richard J. Edwards,et al.  ELM—the database of eukaryotic linear motifs , 2011, Nucleic Acids Res..

[17]  Michael Nilges,et al.  Structural Biology by NMR: Structure, Dynamics, and Interactions , 2008, PLoS Comput. Biol..

[18]  Jaime Prilusky,et al.  FoldIndex copyright: a simple tool to predict whether a given protein sequence is intrinsically unfolded , 2005, Bioinform..

[19]  P. Tompa.  Intrinsically unstructured proteins. , 2002, Trends in biochemical sciences.

[20]  Robert B. Russell,et al.  GlobPlot: exploring protein sequences for globularity and disorder , 2003, Nucleic Acids Res..

[21]  Zoran Obradovic,et al.  DisProt: the Database of Disordered Proteins , 2006, Nucleic Acids Res..

[22]  Kengo Kinoshita,et al.  PrDOS: prediction of disordered protein regions from amino acid sequence , 2007, Nucleic Acids Res..

[23]  G. Vriend,et al.  Exploring Protein Dynamics Space: The Dynasome as the Missing Link between Protein Structure and Function , 2012, PloS one.

[24]  A Keith Dunker,et al.  An assignment of intrinsically disordered regions of proteins based on NMR structures. , 2013, Journal of structural biology.

[25]  Zsuzsanna Dosztányi,et al.  IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content , 2005, Bioinform..

[26]  A Keith Dunker,et al.  A computational investigation of allostery in the catabolite activator protein. , 2007, Journal of the American Chemical Society.

[27]  V. Uversky.  Intrinsically Disordered Proteins , 2014 .

[28]  David S Wishart,et al.  A probabilistic approach for validating protein NMR chemical shift assignments , 2010, Journal of biomolecular NMR.

[29]  P. Radivojac,et al.  PROTEINS: Structure, Function, and Bioinformatics Suppl 7:176–182 (2005) Exploiting Heterogeneous Sequence Properties Improves Prediction of Protein Disorder , 2022 .

[30]  Ian H. Witten,et al.  The WEKA data mining software: an update , 2009, SKDD.

[31]  Zoran Obradovic,et al.  The protein trinity—linking function and disorder , 2001, Nature Biotechnology.

[32]  Pamela D Vise,et al.  Secondary Structure and Dynamics of an Intrinsically Unstructured Linker Domain , 2005, Journal of biomolecular structure & dynamics.

[33]  J. Beckmann,et al.  FoldIndex©: a simple tool to predict whether a given protein sequence is intrinsically unfolded , 2005 .

[34]  W. Vranken,et al.  Validation of archived chemical shifts through atomic coordinates , 2010, Proteins.

[35]  M. DePristo,et al.  Simultaneous determination of protein structure and dynamics , 2005, Nature.

[36]  Adam Godzik,et al.  Between order and disorder in protein structures: analysis of "dual personality" fragments in proteins. , 2007, Structure.

[37]  Rafael Brüschweiler,et al.  Contact model for the prediction of NMR N-H order parameters in globular proteins. , 2002, Journal of the American Chemical Society.

[38]  V. Uversky.  Natively unfolded proteins: A point where biology waits for physics , 2002, Protein science : a publication of the Protein Society.

[39]  Obradovic,et al.  Predicting Protein Disorder for N-, C-, and Internal Regions. , 1999, Genome informatics. Workshop on Genome Informatics.

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

[41]  V. Hilser,et al.  Predicting the energetics of conformational fluctuations in proteins from sequence: a strategy for profiling the proteome. , 2008, Structure.

[42]  K. Teilum,et al.  Functional aspects of protein flexibility , 2009, Cellular and Molecular Life Sciences.

[43]  Christopher J. Oldfield,et al.  The unfoldomics decade: an update on intrinsically disordered proteins , 2008, BMC Genomics.

[44]  J. Gibrat,et al.  Further developments of protein secondary structure prediction using information theory. New parameters and consideration of residue pairs. , 1987, Journal of molecular biology.

[45]  J. L. Goodman,et al.  Relationships between protein structure and dynamics from a database of NMR-derived backbone order parameters. , 2000, Journal of molecular biology.

[46]  Lisa N Kinch,et al.  Optimization of linear disorder predictors yields tight association between crystallographic disorder and hydrophobicity , 2007, Protein science : a publication of the Protein Society.

[47]  Silvio C. E. Tosatto,et al.  ESpritz: accurate and fast prediction of protein disorder , 2012, Bioinform..

[48]  Do-Hyoung Kim,et al.  Understanding pre-structured motifs (PreSMos) in intrinsically unfolded proteins. , 2012, Current protein & peptide science.

[49]  David T. Jones,et al.  Modularity of intrinsic disorder in the human proteome , 2010, Proteins.

[50]  A Keith Dunker,et al.  Exploring the molecular design of protein interaction sites with molecular dynamics simulations and free energy calculations. , 2009, Biochemistry.

[51]  Marc S. Cortese,et al.  Analysis of molecular recognition features (MoRFs). , 2006, Journal of molecular biology.

[52]  István Simon,et al.  Preformed structural elements feature in partner recognition by intrinsically unstructured proteins. , 2004, Journal of molecular biology.

[53]  Reinhard Schweitzer-Stenner,et al.  Conformational propensities and residual structures in unfolded peptides and proteins. , 2012, Molecular bioSystems.

[54]  M. Karplus,et al.  A hierarchy of timescales in protein dynamics is linked to enzyme catalysis , 2007, Nature.