Assessment of conformation and energetics of the N-terminal part of elafinvia computer simulations

Elafin, a specific inhibitor of elastase, is thought to play a regulatory r ole in inflammation. An NMR-derived solution structure of recombinant elafi n has been reported [Francart ct al. (1997) J Mol Biol 268:666 ], although the conformation of its flexible N-terminal part is not established. There is experimental evidence that the N terminus (residues 1-15) of elafin inte racts with the cell membrane. To explore the conformational preferences of residues in this region, we have performed Monte Carlo simulations of the p eptide in water, in cyclohexane, and in a model membrane. Additionally, 3.7 -ns molecular dynamics with explicit water was carried out. The main result s were that the hydrophobic environment stabilizes an alpha helix in the re gion 6-11, the peptide is unordered in water, and it is attached to the mem brane via the amphiphilic alpha -helix 6-11, which inserts with its N termi nus forming an angle of about 60 degrees to the membrane plane. We therefor e assume that in nonpolar media the N-terminal part of elafin forms a short alpha helix which might act as a membrane anchor.