Molecular dynamics simulations of the ErbB-2 transmembrane domain within an explicit membrane environment: comparison with vacuum simulations

Two 500-ps molecular dynamics simulations performed on the single transmemb rane domain of the ErbB-2 tyrosine kinase receptor immersed in a fully solv ated dilauroylphosphatidyl-ethanolamine bilayer (DLPE) are compared to vacu um simulations. One membrane simulation shows that the initial alpha helix undergoes a local pi helix conversion in the peptide part embedded in the m embrane core similar to that found in simulation vacuum. Lipid/water/peptid e interaction analysis shows that in the helix core, the intramolecular pep tide interactions are largely dominant compared to the interactions with wa ter and lipids whereas the helix extremities are much more sensitive to the se interactions at the membrane interfaces. Our results suggest that simula tions in a lipid environment are required to understand the dynamics of tra nsmembrane helices, but can be reasonably supplemented by in vacuo simulati ons to explore rapidly its conformational space and to describe the interna l deformation of the hydrophobic core. (C) 1999 Elsevier Science B.V. All r ights reserved.