Honing the in silico toolkit for detecting protein disorder.

Not all proteins form well defined three-dimensional structures in their native states. Some amino-acid sequences appear to strongly favour the disordered state, whereas some can apparently transition between disordered and ordered states under the influence of changes in the biological environment, thereby playing an important role in processes such as signalling. Although important biologically, for the structural biologist disordered regions of proteins can be disastrous even preventing successful structure determination. The accurate prediction of disorder is therefore important, not least for directing the design of expression constructs so as to maximize the chances of successful structure determination. Such design criteria have become integral to the construct-design strategies of laboratories within the Structural Proteomics In Europe (SPINE) consortium. This paper assesses the current state of the art in disorder prediction in terms of prediction reliability and considers how best to use these methods to guide construct design. Finally, it presents a brief discussion as to how methods of prediction might be improved in the future.

[1]  P. Romero,et al.  Sequence complexity of disordered protein , 2001, Proteins.

[2]  Adam Godzik,et al.  Tolerating some redundancy significantly speeds up clustering of large protein databases , 2002, Bioinform..

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

[4]  M. Saraste,et al.  FEBS Lett , 2000 .

[5]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[6]  S. Vucetic,et al.  Flavors of protein disorder , 2003, Proteins.

[7]  P. Tompa,et al.  The pairwise energy content estimated from amino acid composition discriminates between folded and intrinsically unstructured proteins. , 2005, Journal of molecular biology.

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

[9]  G. Crooks,et al.  WebLogo: a sequence logo generator. , 2004, Genome research.

[10]  T. Gibson,et al.  Protein disorder prediction: implications for structural proteomics. , 2003, Structure.

[11]  Joel L Sussman,et al.  The intracellular domain of the Drosophila cholinesterase‐like neural adhesion protein, gliotactin, is natively unfolded , 2003, Proteins.

[12]  J. S. Sodhi,et al.  Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. , 2004, Journal of molecular biology.

[13]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

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

[15]  G A Petsko,et al.  Aromatic-aromatic interaction: a mechanism of protein structure stabilization. , 1985, Science.

[16]  Marc S. Cortese,et al.  Comparing and combining predictors of mostly disordered proteins. , 2005, Biochemistry.

[17]  V. Uversky,et al.  Why are “natively unfolded” proteins unstructured under physiologic conditions? , 2000, Proteins.

[18]  H. Dyson,et al.  Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. , 1999, Journal of molecular biology.

[19]  Adam Godzik,et al.  Clustering of highly homologous sequences to reduce the size of large protein databases , 2001, Bioinform..

[20]  Marc S. Cortese,et al.  Coupled folding and binding with α-helix-forming molecular recognition elements , 2005 .

[21]  Sameer Velankar,et al.  E-MSD: the European Bioinformatics Institute Macromolecular Structure Database , 2003, Nucleic Acids Res..

[22]  Anne Poupon,et al.  Prediction of unfolded segments in a protein sequence based on amino acid composition , 2005, Bioinform..

[23]  Anna Tempczyk,et al.  Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complex , 1995, Nature.

[24]  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..

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

[26]  김삼묘,et al.  “Bioinformatics” 특집을 내면서 , 2000 .

[27]  P. Tompa.  The interplay between structure and function in intrinsically unstructured proteins , 2005, FEBS letters.