The AMBER lipid force field has been updated to create Lipid14, allowing tensionless simulation of a number of lipid types with the AMBER MD package. The modular nature of this force field allows numerous combinations of head and tail groups to create different lipid types, enabling the easy insertion of new lipid species. The Lennard-Jones and torsion parameters of both the head and tail groups have been revised and updated partial charges calculated. The force field has been validated by simulating bilayers of six different lipid types for a total of 0.5 μs each without applying a surface tension; with favorable comparison to experiment for properties such as area per lipid, volume per lipid, bilayer thickness, NMR order parameters, scattering data, and lipid lateral diffusion. As the derivation of this force field is consistent with the AMBER development philosophy, Lipid14 is compatible with the AMBER protein, nucleic acid, carbohydrate, and small molecule force fields.

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Lipid14: The Amber Lipid Force Field

Water is, of course, a fascinating and important substance. For such a simple molecule, its condensed phase properties are surprisingly complex. Here we might mention the many different solid phases, the higher density of the liquid as compared to ice Ih, and the density maximum (as a function of temperature) in the liquid phase. Moreover, for such a light molecule, many of the liquid-state properties are anomalous: the boiling point, freezing point, heat capacity, surface tension, and viscosity are all unusually high. Even so, it is perhaps surprising that we still do not fully understand the properties of the liquid state.1-3 From a theoretical point of view, this can probably be attributed to two features of liquid water: cooperative hydrogen bonding (H-bonding) and nuclear quantum effects. The former refers to the fact that the binding energy of two H-bonded molecules is modified by the presence of a third molecule.4-9 In terms of simulating the liquid, then, it follows that the potential energy cannot be written as a sum of twomolecule terms. This means that simple two-body simulation models cannot completely describe reality, and attempts to capture the effects of these many-body interactions with polarizable models are not fully satisfactory either.8,10 Nuclear quantum effects occur because the hydrogen nucleus is sufficiently light that classical mechanics for the nuclear motion is simply not adequate. Thus, classical mechanics cannot describe such important properties as spatial dispersion of the hydrogen positions, nuclear tunneling, zero-point energy, and quantization of nuclear motions. Much energy has recently been expended toward the simulation of liquid water using ab initio electronic-structure methods (which, in priniciple, will produce the correct Born-Oppenheimer potential surface, including the effects of many-body interactions),11-19 together with methods for quantum dynamics,19-25 but still more work needs to be done before we have a complete and accurate description.

Vibrational Spectroscopy as a Probe of Structure and Dynamics in Liquid Water

Lipid structural order parameters (reciprocal of fluidity) in biomembranes derived from steady-state fluorescence polarization measurements.

Fluorescence techniques for studying protein structure.

The backbone dynamics of uniformly 15N-labeled interleukin-1 beta are investigated by using two-dimensional inverse detected heteronuclear 15N-1H NMR spectroscopy. 15N T1, T2, and NOE data at a spectrometer frequency of 600 MHz are obtained for 90% of the backbone amide groups. The data provide evidence for motions on three time scales. All the residues exhibit very fast motions on a time scale of approximately less than 20-50 ps that can be characterized by a single-order parameter with an average value of 0.82 +/- 0.05. For a model comprising free diffusion within a cone, these residue-specific order parameters translate to an average cone semiangle of 20.7 +/- 3.3 degrees. Thirty-two residues also display motions on a time scale of 0.5-4 ns, slightly less than the overall rotational correlation time of the protein (8.3 ns). These additional motions must be invoked to account for the discrepancy between experiment and the simplest theoretical formulation in which the internal motions are described by only two parameters, a generalized order parameter and an effective correlation time [Lipari, G., & Szabo, A. (1982a) J. Am. Chem. Soc. 104, 4546-4559]. In particular, while the simple formulation can account for the 15N T1 and T2 data, it fails to account for the 15N-1H NOE data and yields calculated values for the NOEs that are either too small or negative, whereas the observed NOEs are positive. With the introduction of two internal motions that are faster than the rotational correlation time and differ in time scales by at least 1-2 orders of magnitude [Clore, G. M., Szabo, A., Bax, A., Kay, L. E., Driscoll, P. C., & Gronenborn, A. M. (1990) J. Am. Chem. Soc. 112, 4989-4991], all the relaxation data for these 32 residues can be fitted by two order parameters and an effective correlation time for the slower of the two internal motions. A simple model for these two motions is one in which the very fast motion involves axially symmetric diffusion within a cone, while the slower motion comprises jumps between two different orientations of the NH vector. For such a model the jump angle (excluding the C-terminal residue) ranges from 15 degrees to 69 degrees with a mean value of 28.6 +/- 14.0 degrees. Another 42 residues are characterized by some sort of motion on the 30-ns-10-ms time scale, which results in 15N line broadening due to chemical exchange between different conformational substates with distinct 15N chemical shifts.(ABSTRACT TRUNCATED AT 400 WORDS)

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A. Szabo

Papers

Effect of librational motion on fluorescence depolarization and nuclear magnetic resonance relaxation in macromolecules and membranes