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| Jeff Klauda, National Institutes of Health |
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| Jeffery B. Klauda attended Rensselaer Polytechnic Institute for his undergraduate studies and received B.S. degrees in Applied Mathematics and Chemical Engineering in 1998. He then studied under the advisement of Prof. Stanley I. Sandler at the University of Delaware in the Department of Chemical Engineering. His Ph.D. research used ab initio quantum mechanical calculations to obtain thermodynamic properties of gases adsorbing on nanoporous carbons and gas hydrates. The gas hydrate work covered not only the atomic scale but also the global scale and predicted three orders of magnitude more methane trapped in oceanic gas hydrates than conventional methane reserves. After obtaining his Ph.D. in Chemical Engineering in 2003, he is currently an IRTA postdoctoral fellow at the National Institutes of Health under the advisement of Bernard R. Brooks in the National Heart, Lung, and Blood Institute. His current research involves using ab initio calculations to improve the CHARMM lipid force field and studies the structure and dynamics of lipid bilayers using molecular simulations in collaboration with Richard W. Pastor at the Food and Drug Administration.
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Structure of Lipid Membranes and Improving the Head Group Force Field
Jeffery B. Klauda (1), Richard W. Pastor (2) , John F. Nagle (3), and Bernard R. Brooks (1)
(1) Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD20892-8014
(2) Laboratory of Biophysics, Center for Biologics Evaluation and Research, FDA, 1401 Rockville Pike, Rockville, MD 20852-1448
(3) Physics and Biological Sciences Departments, Carnegie Mellon University, Pittsburgh, PA 15213
Molecular dynamics (MD) can be used to better understand the three-dimensional structure of the biologically relevant liquid crystalline (Lalpha) phase. We present ten nanosecond simulations of a dimyristoyl phosphatidylcholine (DMPC) bilayer with five surface areas per lipid (A) (55.0, 59.7, 60.7, 61.7,and 65.0 square Angstroms) and the CHARMM27r (C27r) force field to gain insight into the component structure and the surface area per lipid, A, for DMPC (Aexp=60.6 square Angstroms). Experimentally the distribution of lipid components is obtained from structural models (SM) fit to the data. A new SM is developed based on MD simulations that can directly determine A without the need for assumptions based on gel phase structural properties. This model is fit to experimental form factors and the simulated electron density is in good agreement with experiment, but simulated head group distributions are slightly too broad and the methyl through is elevated.
In addition to slight head group structural inaccuracies, the deuterium order parameters and T1 relaxation times in this region deviate from experiment. The head group portion of the lipid force field is improved using ab initio quantum mechanics (QM) to obtain accurate torsional surface scans of various related small molecules, such as, ethers and portions of the lipid head group. Only the torsional term of the CHARMM forcefield is fit to high-level QM energies. MD simulations with the revised head group force are compared with experimental deuterium order parameters for the glycerol and choline atoms.
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