Temperature- and Length-Dependent Energetics of Formation for Polyalanine Helices in Water:  Assignment of w_Ala(n,T) and Temperature-Dependent CD Ellipticity Standards

Abstract

Length-dependent helical propensities w Ala (n,T) at T = 10, 25, and 60 °C are assigned from t/c values and NMR 13 C chemical shifts for series 1 peptides TrpLys m Inp 2 t Leu-Ala n t LeuInp 2 Lys m NH 2 , n = 15, 19, and 25, m = 5, in water. Van't Hoff analysis of w Ala (n,T) show that α-helix formation is primarily enthalpy-driven. For series 2 peptides Ac-Trp Lys 5 Inp 2 t Leu-β AspHel-Ala nbeta-t LeuInp 2 Lys 5 NH 2 , n = 12 and 22, which contain exceptionally helical Ala n cores, protection factor-derived fractional helicities FH are assigned in the range 10-30 °C in water and used to calibrate temperature-dependent CD ellipticities [θ] λ,H,n,T . These are applied to CD data for series 1 peptides, 12 ≤ n ≤ 45, to confirm the w Ala (n,T) assignments at T = 25 and 60 °C. The [θ] λ,H,n,T are temperature dependent within the wavelength region, 222 ± 12 nm, and yield a temperature correction for calculation of FH from experimental values of [θ] 222,n,T,Exp .

Toward the Design of Highly Efficient, Readily Accessible Peptide N-caps for the Induction of Helical Conformations

“…Firstly, the zero transition is at 201 nm, consistent with literature values for helix standards (Fasman, 1996). Secondly, the [h] 222 /[h] 208 ratio is equal to 1.2, a value close to that recently proposed by the Kemp group (ratio of 1.3) for alanine-rich peptides adopting a complete helical conformation (Heitmann et al, 2005), especially at lower temperatures (Job et al, 2006). N-cap 5, however, also produced a high degree of helicity (89%) when the contribution of the amino acid residues forming the N-cap were neglected in the (Scholtz et al, 1991).…”

Unraveling the Stability of Polypeptide Helices: Critical Role of van der Waals Interactions

“…Only the inclusion of vdW forces can fully explain the remarkable stability of chargecapped polyalanine (Ac-Ala n -LysH þ ) helices up to a temperature of % 725 K as recently observed in gas-phase experiments by Jarrold and co-workers [15]. In contrast, PBE simulations without vdW forces lead to unfolded structures at significantly lower temperatures, being in spurious agreement with solution-phase experiments [26].…”

“…Only the inclusion of vdW forces can fully explain the remarkable stability of chargecapped polyalanine (Ac-Ala n -LysH þ ) helices up to a temperature of % 725 K as recently observed in gas-phase experiments by Jarrold and co-workers [15]. In contrast, PBE simulations without vdW forces lead to unfolded structures at significantly lower temperatures, being in spurious agreement with solution-phase experiments [26].Among the available first-principles methods, densityfunctional theory (DFT) plays a prominent role because it allows for affordable, prolonged molecular dynamics (MD) simulations of condensed matter and molecular systems. DFT with present-day exchange-correlation functionals provides satisfactory accuracy for most covalently and/or hydrogen-bonded systems, and also treats electrostatic and polarization interactions accurately.…”

Comparison of some dispersion-corrected and traditional functionals as applied to peptides and conformations of cyclohexane derivatives

“…The H's that we reported were slightly more stabilizing than those determined by Kemp in experiments done subsequent to our report. 22 Here, we compare the H/residue for folding from an extended strand to an α-helix (see Table II). We have chosen the 17-alanine helix for the comparison.…”