Preston B. Moore

Dynamical Properties of a Hydrated Lipid Bilayer from a Multinanosecond Molecular Dynamics Simulation

A fully hydrated dimiristoylphosphatidylcholine (DMPC) bilayer has been studied by a molecular dynamics simulation. The system, which consisted of 64 DMPC molecules and 1792 water molecules, was run in the NVE ensemble at a temperature of 333 K for a total of 10 ns. The resulting trajectory was used to analyze structural and dynamical quantities. The electron density, bilayer spacing, and order parameters (S(CD)), based on the AMBER forcefield and SPCE water model are in good agreement with previous calculations and experimental data. The simulation reveals evidence for two types of lateral diffusive behavior: cage hopping and that of a two-dimensional liquid. The lateral diffusion coefficient is 8 x 10(-8) cm(2)/s. We characterize the rotational motion, and find that the lipid tail rotation (D(rot_tail) = -0.04 rad(2)/ns) is slower then the head group rotation (D(rot_hg) = 2.2 rad(2)/ns), which is slower than the overall in plane (D(rot) = 3.2 rad(2)/ns) for the lipid molecule.

The low frequency density of states and vibrational population dynamics of polyatomic molecules in liquids

Instantaneous normal mode calculations of the low frequency solvent modes of carbon tetrachloride (CCl4) and chloroform (CHCl3), and experiments on the vibrational population dynamics of the T1u CO stretching mode (∼1980 cm−1) of tungsten hexacarbonyl in CCl4 and CHCl3 are used to understand factors affecting the temperature dependence of the vibrational lifetime. Picosecond infrared pump–probe experiments measuring the vibrational lifetime of the T1u mode from the melting points to the boiling points of the two solvents show a dramatic solvent dependence. In CCl4, the vibrational lifetime decreases as the temperature is increased; however, in CHCl3, the vibrational lifetime actually becomes longer as the temperature is increased. The change in thermal occupation numbers of the modes in the solute/solvent systems cannot account for this difference. Changes in the density of states of the instantaneous normal modes and changes in the magnitude of the anharmonic coupling matrix elements are considered. The ...

Computer simulation studies of biomembranes using a coarse grain model

A computationally efficient coarse grain (CG) model designed to mimic the lipid molecule, dimyristoylphosphatidylcholine (DMPC) is used to study the self-assembly of a lamellar bilayer starting from a disordered configuration. The utility of the CG model is illustrated by examining structural and dynamical properties of a hydrated bilayer system containing 1024 lipid molecules. Comparisons with results for an all-atom model of DMPC suggest that the CG model is about four orders of magnitude less demanding of CPU time.

The M2 channel of influenza A virus: a molecular dynamics study

Molecular dynamics simulations have been performed on a tetramer of the 25‐residue (SSDPLVVAASIIGILHLILWILDRL) synthetic peptide [1] which contains the transmembrane domain of the influenza A virus M2 coat protein. The peptide bundle was initially assembled as a parallel α‐helix bundle in the octane portion of a phase separated water/octane system, which provided a membrane‐mimetic environment. A 4‐ns dynamics trajectory identified a left‐handed coiled coil state of the neutral bundle, with a water filled funnel‐like structural motif at the N‐terminus involving the long hydrophobic sequence. The neck of the funnel begins at V27 and terminates at H37, which blocks the channel. The C‐terminus is held together by inter‐helix hydrogen bonds and contains water below H37. Solvation of the S23 and D24 residues, located at the rim of the funnel, appears to be important for stability of the structure. The calculated average tilt of the helices in the neutral bundle is 27±5°, which agrees well with recent NMR data.

Molecular Dynamics Simulation of a Synthetic Ion Channel

A molecular dynamics simulation has been performed on a synthetic membrane-spanning ion channel, consisting of four alpha-helical peptides, each of which is composed of the amino acids leucine (L) and serine (S), with the sequence Ac-(LSLLLSL)3-CONH2. This four-helix bundle has been shown experimentally to act as a proton-conducting channel in a membrane environment. In the present simulation, the channel was initially assembled as a parallel bundle in the octane portion of a phase-separated water/octane system, which provided a membrane-mimetic environment. An explicit reversible multiple-time-step integrator was used to generate a dynamical trajectory, a few nanoseconds in duration for this composite system on a parallel computer, under ambient conditions. After more than 1 ns, the four helices were found to adopt an associated dimer state with twofold symmetry, which evolved into a coiled-coil tetrameric structure with a left-handed twist. In the coiled-coil state, the polar serine side chains interact to form a layered structure with the core of the bundle filled with H2O. The dipoles of these H2O molecules tended to align opposite the net dipole of the peptide bundle. The calculated dipole relaxation function of the pore H2O molecules exhibits two reorientation times. One is approximately 3.2 ps, and the other is approximately 100 times longer. The diffusion coefficient of the pore H2O is about one-third of the bulk H2O value. The total dipole moment and the inertia tensor of the peptide bundle have been calculated and reveal slow (300 ps) collective oscillatory motions. Our results, which are based on a simple united atom force-field model, suggest that the function of this synthetic ion channel is likely inextricably coupled to its dynamical behavior.

SIMULATION OF THE HIV-1 VPU TRANSMEMBRANE DOMAIN AS A PENTAMERIC BUNDLE

The transmembrane domain of oligomeric protein Vpu encoded by HIV‐1 has been studied by means of a molecular dynamics simulation. A pentameric bundle of unconstrained helices (residues 6–28 of Vpu) with a water filled pore was initially assembled in a membrane mimetic octane/water system. This system was simulated, using the CHARMm19 and OPLS united atom force fields with no constraints at a temperature of 300 K and a pressure of 1 atm. For these forcefields and the initial conditions tested, the oligomeric bundle expelled most of the pore water molecules. The resulting bundle and residual waters adopt a conical structural motif with some resemblance to a potassium channel.

Centroid path integral molecular dynamics simulation of lithium para-hydrogen clusters

The real-time quantum dynamics of a series of lithium para-hydrogen clusters, Li(p-H2)n (n=13, 55, and 180), has been investigated at 2.5 and 4.0 K by means of normal mode centroid path integral molecular dynamics (NMCMD) simulation, following the methodology originally proposed by Cao and Voth [J. Chem. Phys. 101, 6168 (1994)]. The Li(p-H2)34 and neat (p-H2)34 clusters have also been simulated at 2.5 K to see the effect of doping of a Li atom on the cluster dynamics. We explicitly display both the microcanonical and the constant-temperature equations of motion for NMCMD simulations using the Nose–Hoover chain thermostats and the reference system propagator algorithm (RESPA). In addition to the energetic and structural properties, the real-time semi-classical dynamics of the centroids of the Li atom and p-H2 molecules in the clusters has been explored to investigate the diffusive and vibrational properties. In general, quantization of the nuclear motion enhances the ease of melting and diffusion, and also...

A combined instantaneous normal mode and time correlation function description of the infrared vibrational spectrum of ambient water

A formal connection is made between the vibrational density of states (DOS) of a liquid and its approximation by way of instantaneous normal modes (INMs). This analysis leads to a quantum generalization of the INM method (QINM), and to the possibility of evaluating the classical DOS exactly. Further, INM approximations to spectroscopic quantities (e.g., infrared absorption and Raman scattering) follow in a consistent manner by evaluating the appropriate golden rule expressions for harmonic oscillators, using the INM or QINM DOS in place of the true DOS. INM and QINM methods are then applied along with traditional time correlation function (TCF) methods to analyze the entire infrared (IR) spectrum of ambient water. The INM and TCF approaches are found to offer complimentary information. TCF methods are shown to offer an unexpectedly accurate description of the O–H stretching line shape. Further, the 19-fold enhancement in liquid phase absorption compared to the gas phase is also reproduced. INM and QINM methods are used to analyze the molecular origin of the water spectrum, and prove especially effective in analyzing the broad O–H stretching absorption. Further, it is argued that a motional narrowing picture is qualitatively useful in analyzing INM approximations to spectroscopy.

The effect of isotopic substitution and detailed balance on the infrared spectroscopy of water: A combined time correlation function and instantaneous normal mode analysis

We have recently demonstrated that simple classical molecular dynamics methods are capable of nearly quantitatively reproducing most of the intermolecular and intramolecular infrared (IR) spectroscopy of water [H. Ahlborn, X. Ji, B. Space, and P. B. Moore, J. Chem. Phys. 111, 10622 (1999)]. Here it is demonstrated that the result is robust by quantitatively reproducing experimentally measured D2O IR spectroscopy utilizing the same models. This suggests that the quantum effects associated with light atom motion are relatively unimportant. Instantaneous normal mode (INM) theory and the time correlation function (TCF) methodology are used in a complimentary fashion to analyze the molecular origin of the IR spectroscopy of deuterated water (D2O). The TCF methods demonstrate that our models of the dynamics and the system dipole are reasonable by successful quantitative comparison of the theoretical spectrum with experimental results. INM methodology is then employed to analyze what condensed phase motions are ...

Molecular dynamics investigation of membrane-bound bundles of the channel-forming transmembrane domain of viral protein U from the human immunodeficiency virus HIV-1.

Molecular dynamics (MD) simulations have been carried out on bundles of the channel-forming transmembrane (TM) domain of the viral protein U (VPU(1-27) and VPU(6-27)) from the human immunodeficiency virus (HIV-1). Simulations of hexameric and pentameric bundles of VPU(6-27) in an octane/water membrane mimetic system suggested that the pentamer is the preferred oligomer. Accordingly, an unconstrained pentameric helix bundle of VPU(1-27) was then placed in a hydrated palmitoyl-oleyl-3-n-glycero-phosphatidylethanolamine (POPE) lipid bilayer and its structural properties calculated from a 3-ns MD run. Some water molecules, initially inside the channel lumen, were expelled halfway through the simulation and the bundle adopted a conical structure reminiscent of previous MD results obtained for VPU(6-27) in an octane/water system. The pore constriction generated may correspond to a closed state of the channel and underlies the relocation of the W residue toward the pore lumen. The relative positions of the helices with respect to the bilayer and their interactions with the lipids are discussed. The observed structure is stabilized via specific interactions between the VPU helices and the carbonyl oxygen atoms of the lipid molecules, particularly at the Q and S residues.