La. Davies et al., Molecular dynamics simulation of a synthetic four-alpha-helix bundle that binds the anesthetic halothane, FEBS LETTER, 455(3), 1999, pp. 332-338
The structural features of binding sites for volatile anesthetics are exami
ned by performing a molecular dynamics simulation study of the synthetic fo
ur-alpha-helix bundles (A alpha(2))(2), which are formed by association of
two 62-residue di-alpha-helical peptides. The peptide bundle (A alpha(2))(2
) was designed by Johansson et al, [Biochemistry 37 (1998) 1421-1429] and w
as shown experimentally to have a high affinity for the binding of the anes
thetic halothane (CF3CBrClH) in a hydrophobic cavity. Since (A alpha(2))(2)
can exhibit either the anti or syn topologies, the tno distinct bundles ar
e simulated both in the presence and in the absence of halothane, Nanosecon
d length molecular dynamics trajectories were generated for each system at
room temperature (T = 298 K). The structural and dynamic effects of the inc
lusion of halothane are compared, illustrating that the structures are stab
le over the course of the simulation; that the (A alpha(2))(2) bundles have
suitable pockets that can accommodate halothane; that the halothane remain
s in the designed hydrophobic cavity in close proximity to the Trp residues
with a preferred orientation; and that the dimensions of the peptide are p
erturbed by the inclusion of an anesthetic molecule. (C) 1999 Federation of
European Biochemical Societies.