Molecular dynamics simulation of adrenocorticotropin (1-10) peptide in a solvated dodecylphosphocholine micelle

Adrenocorticotropin (ACTH) (1-10), an adrenocorticotropin hormone fragment, has been studied by molecular dynamics (MD) simulation in an NPT ensemble in an explicit dodecylphosphocholine (DPC) micelle. Two starting configurat ions of the peptide/micelle system. corresponding to the insertion and surf ace-binding modes, were used. A common equilibrated configuration, in which the peptide lies parallel to the micellar surface, was reached from both s imulations. In the initial part of the simulations, distance restraints der ived from NMR nuclear Overhauser enhancements were incorporated before the peptide reached an equilibrium configuration with respect to the micelle. A nalyses of the trajectories from the subsequent free (unrestrained) MD simu lation showed that ACTH (1-10) does nor conform strictly to a helical struc ture. The loss of the helical structure is clue to decreased intramolecular hydrogen bonding accompanied by an increase of hydrogen bonding between th e amide protons of the peptide and the micellar head groups. However, the e xtent of the latter interaction is less pronounced than in the negatively c harged SDS micelle. The final structure enhances the amphipathic nature of the peptide, facilitating better interactions at the water-hydrophobic inte rface. The primary hydrophobic interactions with the micelle came from the side chains of Met(4), Phe(7), and Trp(9). All peptide bonds were either hy drated or were involved in intramolecular hydrogen bonding. The interaction s with the DPC micelle, the conformation of the bound peptide, and the dyna mics of the peptide, as revealed bq the rime correlation functions of the N -H bonds, were compared with those of the ACTH (1-10)/SDS system studied pr eviously by MD simulations. (C) 2001 John Wiley & Sons, Inc.