研究领域

Analytical Chemistry/Bioanalytical Chemistry/Bioinorganic Chemistry/Biophysical Chemistry/Chemical Biology/Materials Chemistry/Nano Chemistry/Physical Chemistry/Solid-State NMR Spectroscopy/Structural Biology of Membrane Proteins/Study of Polymers

Membrane proteins act as enzymes, regulate transport processes, and play a central role in intercellular communication. In order to understand the diverse functions of membrane proteins and to engineer these functions for biomedical or biotechnological purposes, it is necessary to determine their high-resolution structure and to describe their dynamics. Structure determination of membrane proteins is one of the most important and challenging aspects of science at the present time. Solid-state NMR spectroscopy is an ideal technique for immobile and non-crystalline proteins that are difficult to study by X-ray crystallography or by solution NMR. The development of solid-state NMR methods and their applications to determine the structure and describe the dynamics of membrane proteins are the main goals of the research program. Biology of the research program involves the preparation of peptides and proteins associated with membranes through synthetic or molecular biological methods. All aspects of sample preparation are optimized including the incorporation of specific and selective isotopic labels, isolation, purification, and final preparation of NMR samples. Antimicrobial peptides, toxins, cytochrome b5, myelin basic protein, and amyloid peptides are some of the systems currently under investigation by this group. Solid-state NMR experiments on membrane proteins incorporated in oriented and unoriented phospholipid bilayers and solution NMR experiments on membrane proteins in detergent micelles or lipid bicelles are performed to determine the structure of membrane proteins. Solid-state NMR spectroscopy is one of the premier methods for studying the structure and dynamics of molecules in solids. Ramamoorthy's research program orchestrates the theoretical design, experimental demonstration, and application of new and cutting edge solid-state NMR spectroscopic methods to study the structure and properties of molecules in single crystalline, liquid crystalline, polycrystalline, and amorphous phases. The design of solid-state NMR methods is composed of a variety of sophisticated techniques including specifically constructed multiple radio-frequency pulses, magic-angle spinning, multiple resonance schemes, sensitivity enhancement procedures, selective observation or hybridization of them. This basic research on spin physics encompasses theoretical and experimental aspects of spin engineering, computer simulations, and instrumentation.

近期论文

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Brender JR, Krishnamoorthy J, Sciacca MF, Vivekanandan S, D'Urso L, Chen J, La Rosa C, Ramamoorthy A. Probing the sources of the apparent irreproducibility of amyloid formation: drastic changes in kinetics and a switch in mechanism due to micellelike oligomer formation at critical concentrations of IAPP. J Phys Chem B. (2015) 119: 2886-96. Link Soblosky L, Ramamoorthy A, Chen Z. Membrane interaction of antimicrobial peptide using E.coli lipid extract as model bacterial cell membranes and SFG spectroscopy. Chem. Phys. Lipids. (in press) Link Lee D, Bhunia A, Kotler SA, Ramamoorthy A. Detergent-type membrane fragmentation by MSI-78, MSI-367, MSI-594, and MSI-843 antimicrobial peptides, and inhibition by cholesterol: a solid-state NMR study. Biochemistry (in press) Link Zhang M, Le Clair SV, Huang R, Ahuja S, Im SC, Waskell L, Ramamoorthy A. Insights into the role of substrates on the interaction between cytochrome b5 and cytochrome P450 2B4 by NMR. Sci. Rep. (Nature) (2015) 5:8392 Link Zhang R, Nishiyama Y, Sun P, Ramamoorthy A, Phase cycling schemes for finite-pulse-RFDR MAS solid-state NMR experiments. J. Magn. Reson. 252 (2015): 55-66 Link Huang R, Zhang M, Rwere F, Waskell L, Ramamoorthy A. Kinetic and structural characterization of the intraction between the FMN binding domain of Cytochrome P450 reductase and cytochrome c. J. Biol. Chem. (in press) Link Yamamoto K, Pearcy P, Lee D, Yu C, Im SC, Waskell L, Ramamoorthy A. Temperature-resistant bicelles for structural studies by solid-state NMR spectroscopy. Langmuir. 31 (2015): 1496-1504 Link Chattah AK, Zhang R, Mroue KH, Pfund LY, Longhi MR, Ramamoorthy A. Investigating albendazole desmotropes by solid-state NMR spectroscopy. Mol Pharm (in press) Link Zhang R., Damron J., Vosegaard T., Ramamoorhty A. A cross-polarization based rotating-frame separated-local-field NMR experiment under ultrafast MAS conditions. J. Magn. Reson. 250 (2015): 37-44 Link Pandey M., Malon M., Ramamoorthy A., Nishiyama Y., Composite-180o pulse-based symmetry sequences to recouple proton Chemical Shift Anisotropy tensors under ultrafast MAS solid-state NMR spectroscopy. J. Magn. Reson. 250 (2015): 45-54 Link Yamamoto K., Caporini MA., Im SC., Waskell L., Ramamoorthy A. Cellular solid-state NMR investigation of a membrane protein using dynamic nuclear polarization. Biochim Biophys Acta. 1848 (2015): 342-349 Link Sudheendra US., Dhople V., Datta A., Kar RK., Shelburne CE., Bhunia A., Ramamoorthy A. Membrane disruptive antimicrobial activities of human β-defensin-3 analogs. Eur J Med Chem. 91 (2015): 91-99 Link DeToma AS., Krishnamoorhty J., Nam YW., Lee HJ., Brender JR., Kochi A., Lee DK., Onnis V., Congiu C., Manfredini S., Vertuani S., Balboni G., Ramamoorthy A., Lim MH., Synthetic Flavonoids, Amonoisoflavones: interaction and reactivity with metal-free and metal-associated amyloid-β species. Chem Sci. 5 (2014): 4851-4862 Link Mroue KH., Zhang R., Zhu P., McNerny E., Kohn DH., Morris MD., Ramamoorhty A., Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA. J Magn Reson. 244 (2014): 90-97 Link Yesuvadian R., Krishnamoorthy J., Ramamoorthy A., Bhunia A., Potent γ-seretase inhibitors/modulators interact with amyloid-β fibrils but do not inhibit fibrillation: a high-resolution NMR study. Biochem Biophy Res Commun. 477(4):590-595 Link Patel H, Pithadia A., Brender J., Fierke C., Ramamoorthy A. In search of aggregation pathways of IAPP and other amyloidogenic proteins: finding answers through NMR spectroscopy. J. Phys. Chem. Lett. 5(11):1864-1870. Link Zhang RC., Ramamoorthy A. Performance of RINEPT is amplified by dipolar couplings under ultrafast MAS conditions. J. Magn Reson. 243(2014):85-92 Link Nishiyama Y., Malon M., Ishii Y., Ramamoorthy A. 3D 15N/15N/1H Chemical shift correlation experiments utilizing an RFDR-based 1H/1H mixing period at 100 kHz MAS. J. Magn Reson. 244(2014):1-5 Link Huang R., Yamamoto K., Zhang M., Popovych N., Hung I., Im SC., Gan ZH., Waskell L., Ramamoorthy A., Probing the transmembrane structure and dynamics of microsomal cytochrome P450 reductase by solid-state NMR, Biophys. J.106(2014), 2126-2133. Nishiyama Y, Zhang R, Ramamoorthy A. Finite-pulse radio frequency driven recoupling with phase cycling for 2D 1H/1H correlation at ultrafast MAS frequencies. J. Magn Reson. 243(2014):25-32 Link