This proposal has three parts, differing in objectives but all involving the study of lipids by X-ray or neutron diffraction. (I) Our crystal structure determinations of cholesteryl esters will be extended to include polar lipids, such as platelet activating factor, phospholipids with unsaturated fatty acid chains and fatty acids related to the hydroxy-eicosatetraenoates. X-ray data from small single crystals will be collected with a synchrotron source at temperatures down to 20 K. The observed conformations of these molecules will provide valuable help in understanding how they assemble in biological membranes and how certain of these lipids function in stimulating a wide range of responses, particularly on the cardiovascular, pulmonary and immune systems. (II) The flexibility of the molecular framework in cholesterol and other lipids will be studied by quasinormal mode analysis. We have recently developed this method for deriving bond torsion force constants from the m.s. displacements of atoms in crystals. Preliminary results suggest that crystallographic data can reveal important molecular dynamical information as well as structure. (III) The charge density in crystals of polar lipid components will be determined by low temperature X-ray and neutron diffraction. Electrostatic properties to be derived experimentally include the electrostatic potential surrounding molecules isolated from the crystal structure, the molecular dipole moment and the electrostatic interaction energies for molecular assemblies. Such properties are particularly important for the polar lipids because Columbic forces and H-bond are the major factors determining first the arrangement of the head groups in biological membranes and second the interaction of these surface groups with ions and water of hydration.

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National Heart, Lung, and Blood Institute (NHLBI)
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Molecular and Cellular Biophysics Study Section (BBCA)
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University of Pittsburgh
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Luo, J Q; Ruble, J R; Craven, B M et al. (1996) Effects of H/D substitution on thermal vibrations in piperazinium hexanoate-h11, d11. Acta Crystallogr B 52 ( Pt 2):357-68
Luo, J Q; Ruble, J R; Craven, B M (1995) Crystal structure of piperazinium oleate at -150 degrees C. J Lipid Res 36:332-42
Kampermann, S P; Sabine, T M; Craven, B M et al. (1995) Hexamethylenetetramine: extinction and thermal vibrations from neutron diffraction at six temperatures. Acta Crystallogr A 51 ( Pt 4):489-97
Langs, D A; Miller, R; Hauptman, H A et al. (1995) Use of the minimal function for partial structure development in direct methods. Acta Crystallogr A 51 ( Pt 1):81-7
Han, G W; Ruble, J R; Craven, B M (1994) The crystal structure of 1,2-dipalmitoyl-sn-glycerol at 123 K. Chem Phys Lipids 71:219-28
Gao, Q; Weber, H P; Craven, B M et al. (1994) Structure of suberic acid at 18.4, 75 and 123 K from neutron diffraction data. Acta Crystallogr B 50 ( Pt 6):695-703
Kampermann, S P; Ruble, J R; Craven, B M (1994) The charge-density distribution in hexamethylenetetramine at 120 K. Acta Crystallogr B 50 ( Pt 6):737-41
Han, G W; Craven, B M; Langs, D A (1994) Crystal structure of cholesteryl butanoate at 123 K. J Lipid Res 35:2069-82
Terpstra, M; Craven, B M; Stewart, R F (1993) Hexamethylenetetramine at 298 K: new refinements. Acta Crystallogr A 49 ( Pt 5):685-92
He, X M; Craven, B M (1993) Internal vibrations of a molecule consisting of rigid segments. I. Non-interacting internal vibrations. Acta Crystallogr A 49 ( Pt 1):10-22

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