The long term goal of this program is to relate protein structure and dynamics to function. There are two principal objectives in this competing renewal. The first objective centers on the demonstration that fluorescence anisotropy decays can be used to detect conformational substates. The achievement of this particular goal will require the development of improved methods of analysis of anisotropy data, especially for detection and quantification of picosecond correlation times; development of alternate interpretative models and procedures; creation of optimal protein models bearing single fluorphors; and using molecular dynamics/mechanics simulations to assess the molecular motions predicted by analysis of anisotropy data. The second major objective focuses on the evaluation of properties of water in the lipid binding cavity of intestinal fatty acid binding protein. This cavity and the water within will be characterized by X-filtered NOESY and ROESY NMR measurements and by nuclear magnetic relaxation dispersion techniques; molecular dynamics and electrostatic calculations; structural analysis of IFABP-fluorophor complexes and covalent adducts and their comparison to obtained fluorescence measurements of dipolar relaxation rates.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular and Cellular Biophysics Study Section (BBCA)
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Wehrle, Janna P
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Mayo Clinic, Rochester
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Kamlekar, Ravi Kanth; Simanshu, Dhirendra K; Gao, Yong-guang et al. (2013) The glycolipid transfer protein (GLTP) domain of phosphoinositol 4-phosphate adaptor protein-2 (FAPP2): structure drives preference for simple neutral glycosphingolipids. Biochim Biophys Acta 1831:417-27
Kenoth, Roopa; Kamlekar, Ravi Kanth; Simanshu, Dhirendra K et al. (2011) Conformational folding and stability of the HET-C2 glycolipid transfer protein fold: does a molten globule-like state regulate activity? Biochemistry 50:5163-71
Kamlekar, Ravi Kanth; Gao, Yongguang; Kenoth, Roopa et al. (2010) Human GLTP: Three distinct functions for the three tryptophans in a novel peripheral amphitropic fold. Biophys J 99:2626-35
Kenoth, Roopa; Simanshu, Dhirendra K; Kamlekar, Ravi Kanth et al. (2010) Structural determination and tryptophan fluorescence of heterokaryon incompatibility C2 protein (HET-C2), a fungal glycolipid transfer protein (GLTP), provide novel insights into glycolipid specificity and membrane interaction by the GLTP fold. J Biol Chem 285:13066-78
Kirk, William (2008) Solvent Stokes'shifts revisited: application and comparison of Thompson-Schweizer-Chandler-Song-Marcus theories with Ooshika-Bakshiev-Lippert theories. J Phys Chem A 112:13609-21
Kirk, William; Klimtchuk, Elena (2007) Photophysics of ANS. III: Circular dichroism of ANS and anilinonaphthalene in I-FABP. Biophys Chem 125:24-31
Kirk, William (2007) Photophysics of ANS. II: Charge transfer character of near-UV absorption and consequences for ANS spectroscopy. Biophys Chem 125:13-23
Kirk, William; Kurian, Elizabeth; Wessels, William (2007) Photophysics of ANS. V. Decay modes of ANS in proteins: the IFABP-ANS complex. Biophys Chem 125:50-8
Klimtchuk, Elena; Venyaminov, Sergei; Kurian, Elizabeth et al. (2007) Photophysics of ANS. I. Protein-ANS complexes: Intestinal fatty acid binding protein and single-trp mutants. Biophys Chem 125:1-12
Kirk, William; Wessels, William (2007) Photophysics of ANS. IV. Electron transfer quenching of ANS in alcoholic solvents and mixtures. Biophys Chem 125:32-49

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