Conformational Analysis of α-Helical Polypeptides in Two Opposite Screw Forms. A Combined Use of 2H NMR and MD Simulation

Abstract

In this work, we wish to report the results of conformational analysis of poly(β-phenethyl L-aspartate) (PPLA) and poly(γ-benzyl L-glutamate) (PBLG) in two opposite α-helical screw sense. Variously deuterated PPLA samples were prepared, and 2H NMR measurements were carried out in tetrachloroethane at two different temperatures: one for the right-handed and the other for the left-handed α-helical state. The rotational isomeric state (RIS) analysis of the 2H NMR quadrupolar splitting data was carried out, and the sidechain conformations were estimated. The results of the analysis for the right-handed α-helical PBLG have been reported previously. In the right-handed α-helix regime, i.e., r-PPLA and r-PBLG, the preferred form of the first two bonds was found to be χ1χ2=tt, leading to an extended sidechain conformation in the direction perpendicular to the α-helical axis. The corresponding arrangements in the l-form (1-PPLA) are more or less evenly distributed among three states, g−t, tt, and g−g+. MD simulations were performed for the side chain flanking the right- and left-handed α-helical backbone by using Biosym’s Discover program. An α-helix fragment consisting of 18 aminoacid residues, Ac-X18-NHMe with X= Asp(OPhe) or Glu(OBzl), was adopted as a model for the polymers in the simulation. The preferred sidechain conformations were elucidated as an average over an interval 100—200 ps. The simulations were performed in vacuo as well as in the presence of solvent molecules (chloroform). The agreement was found to be quite reasonable in all three polymer systems for which relevant experimental data are available.