Rg. Efremov et al., Assessment of conformation and energetics of the N-terminal part of elafinvia computer simulations, THEOR CH AC, 106(1-2), 2001, pp. 55-61
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.