Molecular dynamics simulation of a synthetic four‐α‐helix bundle that binds the anesthetic halothane

FEBS Letters

Klein, Michael L.²  Scharf, Daphna¹  Davies, Lowri A.² 

[1]Department of Anesthesia, University of Pennsylvania Medical Center, Philadelphia, PA 19104-4283, USA

[2]Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA

关键词: Molecular dynamics simulation;    Synthetic four-α-helix bundle;    Halothane;   

DOI  :  10.1016/S0014-5793(99)00890-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The structural features of binding sites for volatile anesthetics are examined by performing a molecular dynamics simulation study of the synthetic four-α-helix bundles (Aα₂)₂, which are formed by association of two 62-residue di-α-helical peptides. The peptide bundle (Aα₂)₂ was designed by Johansson et al. [Biochemistry 37 (1998) 1421–1429] and was shown experimentally to have a high affinity for the binding of the anesthetic halothane (CF₃CBrClH) in a hydrophobic cavity. Since (Aα₂)₂ can exhibit either the anti or syn topologies, the two distinct bundles are simulated both in the presence and in the absence of halothane. Nanosecond length molecular dynamics trajectories were generated for each system at room temperature (T=298 K). The structural and dynamic effects of the inclusion of halothane are compared, illustrating that the structures are stable over the course of the simulation; that the (Aα₂)₂ bundles have suitable pockets that can accommodate halothane; that the halothane remains in the designed hydrophobic cavity in close proximity to the Trp residues with a preferred orientation; and that the dimensions of the peptide are perturbed by the inclusion of an anesthetic molecule.

【 授权许可】

Unknown