title: The helical alanine controversy: an (Ala)6 insertion dramatically increases helicity.
abstract: Employing chemical shift melts and hydrogen/deuterium exchange NMR techniques, we have determined the stabilization of the Trp-cage miniprotein due to multiple alanine insertions within the N-terminal alpha-helix. Alanine is shown to be uniquely helix-stabilizing and this stabilization is reflected in the global fold stability of the Trp-cage. The associated free energy change per alanine can be utilized to calculate the alanine propagation value. From the Lifson-Roig formulation, the calculated value (wAla = 1.6) is comparable to those obtained for short, solubilized, alanine-rich helices and is much larger than the values obtained by prior host-guest techniques or in N-terminally templated helices and peptides bearing long contiguous strings of alanines with no capping or solubilizing units present.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Jasper C
authors.initials: JC
authors.lastname: Lin
authors.forename: Bipasha
authors.initials: B
authors.lastname: Barua
authors.forename: Niels H
authors.initials: NH
authors.lastname: Andersen
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D010455:Peptides; C019529:polyalanine; D014364:Tryptophan; D000409:Alanine