Molecular dynamics simulation of membranes and a transmembrane helix

Three molecular dynamics (MD) simulations of 1.5-ns length were carried out on fully hydrated patches of dimyristoyl phosphatidylcholine (DMPC) bilaye rs in the liquid-crystalline phase. The simulations were performed using di fferent ensembles and electrostatic conditions: a microcanonical ensemble o r constant pressure-temperature ensemble, with or without truncated electro static interactions. Calculated properties of the membrane patches from the three different protocols were compared to available data from experiments . These data include the resulting overall geometrical dimensions, the orde r characteristics of the lipid hydrocarbon chains, as well as various measu res of the conformations of the polar head groups. The comparisons indicate that the simulation carried out within the microcanonical ensemble with tr uncated electrostatic interactions yielded results closest to the experimen tal data, provided that the initial equilibration phase preceding the produ ction run was sufficiently long. The effects of embedding a non-ideal helic al protein domain in the membrane patch were studied with the same MD proto cols. This simulation was carried out for 2.5 ns. The protein domain corres ponds to the seventh transmembrane segment (TMS7) of the human serotonin 5H T(2A) receptor. The peptide is composed of two alpha-helical segments linke d by a hinge domain around a perturbing Asn-Pro motif that produces at the end of the simulation a kink angle of nearly 80 degrees between the two hel ices. Several aspects of the TMS7 structure, such as the bending angle, bac kbone Phi, and Psi torsion angles, the intramolecular hydrogen bonds, and t he overall conformation, were found to be very similar to those determined by NMR for the corresponding transmembrane segment of the tachykinin NK-I r eceptor. In general, the simulations were found to yield structural and dyn amic characteristics that are in good agreement with experiment. These find ings support the application of simulation methods to the study of the comp lex biomolecular systems at the membrane interface Of cells. (C) 1999 Acade mic Press.