Studying the stability of a helical β-heptapeptide by molecular dynamics simulations

Abstract

β-Peptides consisting entirely of homochiral β-amino acids R-CH(NH2)-CH2CO2H form 31-helices in solution, as shown previously by NMR analysis of pyridine and methanol solutions. The stability of the helical secondary structure of one such β-peptide (H-β-HVal-β-HAla-β-HLeu-(S,S)-β-HAIa(αMe)-β-HVal-β-HAla-β-HLeu-OH, 1) has been investigated by molecular dynamics simulations using the GROMOS 96 molecular model and force field (962 methanol molecules; T=298, 350, 400K; with and without NOE distance restraints). The restraints derived from the NMR studies were equally well satisfied by both the re-strained and the unrestrained room-temperature molecular dynamics simulations. The 31-helical conformation of 1 was shown to be so stable that it was restored spontaneously within 400 ps after unfolding had been induced by a sudden increase of the temperature from 298 to 350 K.