Next Article in Journal
Emerging Mechanistic Insights into AAA Complexes Regulating Proteasomal Degradation
Next Article in Special Issue
Probing the Kinetic Stabilities of Friedreich’s Ataxia Clinical Variants Using a Solid Phase GroEL Chaperonin Capture Platform
Previous Article in Journal
Chaperoning Proteins for Destruction: Diverse Roles of Hsp70 Chaperones and their Co-Chaperones in Targeting Misfolded Proteins to the Proteasome
Previous Article in Special Issue
Decoding F508del Misfolding in Cystic Fibrosis
Open AccessReview

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

Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19026, USA
Author to whom correspondence should be addressed.
Biomolecules 2014, 4(3), 725-773;
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)
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
Show Figures

Figure 1

MDPI and ACS Style

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

Show more citation formats Show less citations formats

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.
Back to TopTop