This proposal is for a competitive revision, under NCRR funding announcement: PAR-12-046, of the parent grant R41RR016292 funding, P41 Center: National Biomedical Center for Advanced ESR Technology. This proposal is for a new technology project, not included on the parent grant, but which greatly benefits the aims of the parent grant, in particular Technology Research and Development (TR&D) Project: Structure of Proteins and Protein Complexes by Pulse Dipolar ESR (PDS-ESR), which is concerned with improving existing and developing new distance measurement techniques for structural studies on biomolecules. The new project is to develop methods of composite pulses, common in NMR, to be applied to ESR, which requires much shorter pulse widths and is subject to much faster spin-relaxation. This is now possible using a new Tektronix Arbitrary Waveform Generator (AWG) that will enable the modulation of the microwave pulses with sub-ns resolution. It will enable better spectral coverage by the pulses in the double-quantum coherence (DQC)-ESR method for distance measurements, which requires non-selective pulses. It will enable well-designed selective pulses required for the double electron-electron resonance (DEER) method. This will enhance signal-to-noise and suppression of unwanted signals and artifacts, thereby improving these methodologies. The AWG will be integrated into the pulse ESR spectrometer with due consideration of the letter's detailed performance. Monitoring of the composite pulsing at key positions in the microwave bridge, with the help of a sufficiently wide-bandwidth digital sampling oscilloscope (DSO), will permit automatic retuning of the AWG to modify as needed the composite pulses to guarantee the quality of the pulses that actually reach the sample. This project will involve a synergistic interaction, driven by the needs of the Driving Biomedical Projects (DBP's) as in the Parent Grant. Careful tests will be made of this new composite-pulse technology to demonstrate how it significantly improves the distance measurements and allows new and more challenging studies included in the DBP's to be carried out.

Public Health Relevance

This is a revision to the BTRC, which supports NIH sponsored projects aimed at understanding and combating diseases and ailments (e.g. cancer, cardiac disease, AIDS, neurological disorders, Parkinsons, Alzheimers, Hodgkins, Wernicke Encephlopathy, depressive disorders and Schizophrenia, P. aeruginosa lung infections, Ebola viral infections, and allergies) by studying the structure and function of key proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
3P41GM103521-12S1
Application #
8417782
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (40))
Program Officer
Friedman, Fred K
Project Start
2012-09-01
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
12
Fiscal Year
2012
Total Cost
$414,600
Indirect Cost
$107,172
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Srivastava, Madhur; Freed, Jack H (2018) Singular Value Decomposition Method to Determine Distance Distributions in Pulse Dipolar Electron Spin Resonance: II. Estimating Uncertainty. J Phys Chem A :
Selmke, Benjamin; Borbat, Peter P; Nickolaus, Chen et al. (2018) Open and Closed Form of Maltose Binding Protein in Its Native and Molten Globule State As Studied by Electron Paramagnetic Resonance Spectroscopy. Biochemistry 57:5507-5512
Riederer, Erika A; Focke, Paul J; Georgieva, Elka R et al. (2018) A facile approach for the in vitro assembly of multimeric membrane transport proteins. Elife 7:
Vilbert, Avery C; Caranto, Jonathan D; Lancaster, Kyle M (2018) Influences of the heme-lysine crosslink in cytochrome P460 over redox catalysis and nitric oxide sensitivity. Chem Sci 9:368-379
Merz, Gregory E; Borbat, Peter P; Muok, Alise R et al. (2018) Site-Specific Incorporation of a Cu2+ Spin Label into Proteins for Measuring Distances by Pulsed Dipolar Electron Spin Resonance Spectroscopy. J Phys Chem B 122:9443-9451
Cooper, Rebecca S; Georgieva, Elka R; Borbat, Peter P et al. (2018) Structural basis for membrane anchoring and fusion regulation of the herpes simplex virus fusogen gB. Nat Struct Mol Biol 25:416-424
Smith, Meghan A; Lancaster, Kyle M (2018) The Eponymous Cofactors in Cytochrome P460s from Ammonia-Oxidizing Bacteria Are Iron Porphyrinoids Whose Macrocycles Are Dibasic. Biochemistry 57:334-343
Meirovitch, Eva; Liang, Zhichun; Freed, Jack H (2018) MOMD Analysis of NMR Line Shapes from A?-Amyloid Fibrils: A New Tool for Characterizing Molecular Environments in Protein Aggregates. J Phys Chem B 122:4793-4801
Siu, Juno C; Sauer, Gregory S; Saha, Ambarneil et al. (2018) Electrochemical Azidooxygenation of Alkenes Mediated by a TEMPO-N3 Charge-Transfer Complex. J Am Chem Soc 140:12511-12520
Meirovitch, Eva; Liang, Zhichun; Freed, Jack H (2018) Phenyl-Ring Dynamics in Amyloid Fibrils and Proteins: The Microscopic-Order-Macroscopic-Disorder Perspective. J Phys Chem B 122:8675-8684

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