This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.105.075697v1 90/8/2796    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klauda, J. B. Articles by Nagle, J. F. Search for Related Content PubMed PubMed Citation Articles by Klauda, J. B. Articles by Nagle, J. F.

Simulation-Based Methods for Interpreting X-Ray Data from Lipid Bilayers

Jeffery B. Klauda ^*, Norbert Kuerka , Bernard R. Brooks ^*, Richard W. Pastor  and John F. Nagle 

^* Laboratory of Computational Biology, National Institutes of Health, Bethesda, Maryland 20892; Physics and Biological Sciences Departments, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213; and Laboratory of Biophysics, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland 20852-1448

Correspondence: Address reprint requests to Jeffery B. Klauda, E-mail: klauda{at}helix.nih.gov.

The fully hydrated liquid crystalline phase of the dimyristoylphosphatidycholine lipid bilayer at 30°C was simulated using molecular dynamics with the CHARMM potential for five surface areas per lipid (A) in the range 55–65 Ų that brackets the previously determined experimental area 60.6 Ų. The results of these simulations are used to develop a new hybrid zero-baseline structural model, denoted H2, for the electron density profile, (z), for the purpose of interpreting x-ray diffraction data. H2 and also the older hybrid baseline model were tested by fitting to partial information from the simulation and various constraints, both of which correspond to those available experimentally. The A, (z), and F(q) obtained from the models agree with those calculated directly from simulation at each of the five areas, thereby validating this use of the models. The new H2 was then applied to experimental dimyristoylphosphatidycholine data; it yields A = 60.6 ± 0.5 Ų, in agreement with the earlier estimate obtained using the hybrid baseline model. The electron density profiles also compare well, despite considerable differences in the functional forms of the two models. Overall, the simulated (z) at A = 60.7 Ų agrees well with experiment, demonstrating the accuracy of the CHARMM lipid force field; small discrepancies indicate targets for improvements. Lastly, a simulation-based model-free approach for obtaining A is proposed. It is based on interpolating the area that minimizes the difference between the experimental F(q) and simulated F(q) evaluated for a range of surface areas. This approach is independent of structural models and could be used to determine structural properties of bilayers with different lipids, cholesterol, and peptides.

This article has been cited by other articles:

				J. Pan, S. Tristram-Nagle, N. Kucerka, and J. F. Nagle Temperature Dependence of Structure, Bending Rigidity, and Bilayer Interactions of Dioleoylphosphatidylcholine Bilayers Biophys. J., January 1, 2008; 94(1): 117 - 124. [Abstract] [Full Text] [PDF]

				J. C. Mathai, S. Tristram-Nagle, J. F. Nagle, and M. L. Zeidel Structural Determinants of Water Permeability through the Lipid Membrane J. Gen. Physiol., December 31, 2007; 131(1): 69 - 76. [Abstract] [Full Text] [PDF]

				J. F. Nagle, J. C. Mathai, M. L. Zeidel, and S. Tristram-Nagle Theory of Passive Permeability through Lipid Bilayers J. Gen. Physiol., December 31, 2007; 131(1): 77 - 85. [Abstract] [Full Text] [PDF]

				H. D. Herce and A. E. Garcia Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes PNAS, December 26, 2007; 104(52): 20805 - 20810. [Abstract] [Full Text] [PDF]

				J. Sonne, M. O. Jensen, F. Y. Hansen, L. Hemmingsen, and G. H. Peters Reparameterization of All-Atom Dipalmitoylphosphatidylcholine Lipid Parameters Enables Simulation of Fluid Bilayers at Zero Tension Biophys. J., June 15, 2007; 92(12): 4157 - 4167. [Abstract] [Full Text] [PDF]

				S. H. White Membrane Protein Insertion: The Biology-Physics Nexus J. Gen. Physiol., April 30, 2007; 129(5): 363 - 369. [Full Text] [PDF]

				S. A. Pandit, S.-W. Chiu, E. Jakobsson, A. Grama, and H. L. Scott Cholesterol Surrogates: A Comparison of Cholesterol and 16:0 Ceramide in POPC Bilayers Biophys. J., February 1, 2007; 92(3): 920 - 927. [Abstract] [Full Text] [PDF]

				N. Kucerka, S. Tristram-Nagle, and J. F. Nagle Closer Look at Structure of Fully Hydrated Fluid Phase DPPC Bilayers Biophys. J., June 1, 2006; 90(11): L83 - L85. [Abstract] [Full Text] [PDF]