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Biomolecules 2014, 4(3), 725-773; doi:10.3390/biom4030725

Local Order in the Unfolded State: Conformational Biases and Nearest Neighbor Interactions

Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19026, USA
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Received: 4 February 2014 / Revised: 17 June 2014 / Accepted: 20 June 2014 / Published: 24 July 2014
(This article belongs to the Special Issue Protein Folding and Misfolding)

Abstract

The discovery of Intrinsically Disordered Proteins, which contain significant levels of disorder yet perform complex biologically functions, as well as unwanted aggregation, has motivated numerous experimental and theoretical studies aimed at describing residue-level conformational ensembles. Multiple lines of evidence gathered over the last 15 years strongly suggest that amino acids residues display unique and restricted conformational preferences in the unfolded state of peptides and proteins, contrary to one of the basic assumptions of the canonical random coil model. To fully understand residue level order/disorder, however, one has to gain a quantitative, experimentally based picture of conformational distributions and to determine the physical basis underlying residue-level conformational biases. Here, we review the experimental, computational and bioinformatic evidence for conformational preferences of amino acid residues in (mostly short) peptides that can be utilized as suitable model systems for unfolded states of peptides and proteins. In this context particular attention is paid to the alleged high polyproline II preference of alanine. We discuss how these conformational propensities may be modulated by peptide solvent interactions and so called nearest-neighbor interactions. The relevance of conformational propensities for the protein folding problem and the understanding of IDPs is briefly discussed. View Full-Text
Keywords: unfolded; peptide conformation; pPII; nearest-neighbor; alanine unfolded; peptide conformation; pPII; nearest-neighbor; alanine
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Toal, S.; Schweitzer-Stenner, R. Local Order in the Unfolded State: Conformational Biases and Nearest Neighbor Interactions. Biomolecules 2014, 4, 725-773.

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