AN INVESTIGATION OF THE CONFORMATION OF PEPTIDE-T AND ITS D-ALA ANALOG BY NMR AND MOLECULAR-DYNAMICS SIMULATIONS

Peptide-T (ASTTTNYT) and its D-Ala analog (D-ASTTTNYT-NH2) have been d esigned to block the adsorption of HIV to CD4 receptors on T-cell lymp hocytes, thus inhibiting viral infectivity. The conformation of these important peptides has been investigated by 2D-NMR and molecular dynam ics simulations. The NMR studies in DMSO show that the peptides exist in solution as a mixture of conformations. beta-Turns and non-specific folded conformations are present in a small proportion in the ensembl e of conformations, which is largely dominated by more or less extende d structures. This result is in line with molecular dynamics simulatio ns where beta-turns were found to occur with a low frequency and with energies 10 to 17 kcal/mole higher than the global minimum structure. Our findings differ from previous reports on the conformation of pepti de-T determined by NMR.