STUDYING THE STABILITY OF A HELICAL BETA-HEPTAPEPTIDE BY MOLECULAR-DYNAMICS SIMULATIONS

beta-Peptides consisting entirely of homochiral beta-amino acids R-CH( NH2)-CH2CO2H form 3(1)-helices in solution, as shown previously by NMR analysis of pyridine and methanol solutions. The stability of the hel ical secondary structure of one such beta-peptide eta-HVal-beta-HAla-b eta-HLeu-(S,S)-beta-HAla(alpha Me)-beta-HVal-beta- HAla-beta-HLeu-OH, 1) has been investigated by molecular dynamics simulations using the G ROMOS96 molecular model and force field (962 methanol molecules: T = 2 98, 350, 400 K; with and without NOE distance restraints). The restrai nts derived from the NMR studies were equally well satisfied by both t he restrained and the unrestrained room-temperature molecular dynamics simulations. The 3(1)-helical conformation of 1 was shown to be so st able that it was restored spontaneously within 400 ps after unfolding had been induced by a sudden increase of the temperature from 298 to 3 50 K.