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DEER spectroscopy tools for probing protein conformational dynamics

Award Number: R35GM151956
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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DEER spectroscopy tools for probing protein conformational dynamics - PROJECT SUMMARY/ABSTRACT This project develops new experimental and computational methods for DEER (double electron- electron resonance) spectroscopy. DEER is a biostructural technique for the quantification of protein conformational landscapes and protein motions on the nanometer scale. Protein motions are crucial for many key molecular processes at the basis of human life and disease. Therefore, DEER provides important insights that contribute to the knowledge base necessary for drug development. In combination with X-ray crystallography, cryo-EM, NMR, FRET and others, DEER is part of a complementary set of integrative experimental biostructural tools. It is especially important for the study of membrane proteins. Several major barriers exist in the field: the lack of integrated analysis and modeling tools for biomedical researchers, and the lack of experimental approaches for studying proteins in their native cellular environment. This project directly addresses these issues as it aims to (a) develop methods and tools based on Bayesian statistics and deep learning for the rigorous and reproducible analysis of experimental DEER data; (b) create advanced computational approaches that utilize DEER data for modeling proteins; (c) develop methodology based on noncanonical amino acids for labeling proteins directly in their cellular environment; (d) advance a rapid freeze quench approach to measure conformational dynamics down to the sub-millisecond time scale. Overall, the goal of the project is to significantly expand the scope of DEER by providing innovative approaches to data analysis, modeling, and in-cell and time-resolved measurements. This will enable the study of the structure and dynamics of larger and more complex proteins and protein assemblies in the cellular environment. This is of increasing importance in biomedical research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $377,238 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	3	2/10/2026	NON-COMPETING CONTINUATION	$377,238
														Subtotal = $377,238

Issue Date FY: 2025 ( Subtotal = $377,238 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	002	2	7/16/2025	NON-COMPETING CONTINUATION	$0
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	2	5/29/2025	NON-COMPETING CONTINUATION	$377,238
2025	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	1	11/25/2024	NEW	$0
														Subtotal = $377,238

Issue Date FY: 2024 ( Subtotal = $645,528 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	1	1/31/2024	NEW	$461,697
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	1	6/26/2024	SUPPLEMENT FOR EXPANSION	$183,831
														Subtotal = $645,528

Grand Total All Awards = $1,400,004

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DEER spectroscopy tools for probing protein conformational dynamics

Award Number: R35GM151956

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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