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The protein trinity - linking function and disorder
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••], this paper used theoretical predictions and experiments to test the prediction that highly polar, uncharged sequences collapse despite their lack of hydrophobic residues. This collapse occurs for a variety of polar uncharged sequences and even for the backbone alone. Thus, it is likely to be a general result that arises because water is such a poor solvent for both the backbone and certain polar polypeptide chains.
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••], this paper used theoretical predictions and experiments to test the prediction that highly polar, uncharged sequences collapse despite their lack of hydrophobic residues. This collapse occurs for a variety of polar uncharged sequences and even for the backbone alone. Thus, it is likely to be a general result that arises because water is such a poor solvent for both the backbone and certain polar polypeptide chains.
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Uversky V.N. Protein folding revisited. A polypeptide chain at the folding-misfolding-nonfolding cross-roads: which way to go?. Cell Mol Life Sci 60 (2003) 1852-1871
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Proceedings of the International Conference on Neural Networks
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Why are "natively unfolded" proteins unstructured under physiologic conditions?
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Uversky V.N., Gillespie J.R., and Fink A.L. Why are "natively unfolded" proteins unstructured under physiologic conditions?. Proteins 41 (2000) 415-427
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Intrinsic disorder and functional proteomics
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Radivojac P., Iakoucheva L.M., Oldfield C.J., Obradovic Z., Uversky V.N., and Dunker A.K. Intrinsic disorder and functional proteomics. Biophys J 92 (2007) 1439-1456
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The CASP assessment papers are worth reading. Various researchers claim that one predictor or another (usually their own) is better than the others. The CASP exercises are evaluations based on blind predictions, and the evaluations are by third parties, so the comparisons are less biased. However, the CASP exercises involve only a small number of proteins, so claims to have developed 'the best predictor' should not be made on their basis either.
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Bordoli L., Kiefer F., and Schwede T. Assessment of disorder predictions in CASP7. Proteins 69 Suppl 8 (2007) 129-136. The CASP assessment papers are worth reading. Various researchers claim that one predictor or another (usually their own) is better than the others. The CASP exercises are evaluations based on blind predictions, and the evaluations are by third parties, so the comparisons are less biased. However, the CASP exercises involve only a small number of proteins, so claims to have developed 'the best predictor' should not be made on their basis either.
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Dunker A.K., Obradovic Z., Romero P., Garner E.C., and Brown C.J. Intrinsic protein disorder in complete genomes. Genome Inform Ser Workshop Genome Inform 11 (2000) 161-171
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Dynamic behavior of an intrinsically unstructured linker domain is conserved in the face of negligible amino acid sequence conservation
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This paper reminds us that not all functions associated with disorder involve binding to a partner, and shows that features likely to be of functional importance, such as length and flexibility, can be conserved in the face of lack of amino acid sequence conservation.
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Daughdrill G.W., Narayanaswami P., Gilmore S.H., Belczyk A., and Brown C.J. Dynamic behavior of an intrinsically unstructured linker domain is conserved in the face of negligible amino acid sequence conservation. J Mol Evol 65 (2007) 277-288. This paper reminds us that not all functions associated with disorder involve binding to a partner, and shows that features likely to be of functional importance, such as length and flexibility, can be conserved in the face of lack of amino acid sequence conservation.
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Fiorin G., Biekofsky R.R., Pastore A., and Carloni P. Unwinding the helical linker of calcium-loaded calmodulin: a molecular dynamics study. Proteins 61 (2005) 829-839
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This paper shows the power of Raman optical activity to distinguish between intrinsically unfolded sequences and sequences that fold into structures that are often difficult to differentiate from them, such as the polyproline-II fold.
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These results were a big surprise; most expected unfolded proteins to be degraded faster than structured proteins. Intracellular protein lifetimes vary over at least 12 orders of magnitude. Evidently a number of factors, including protein disorder, contribute to intracellular protein lifetimes.
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