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Integrated tools for higher order structure determination by cross-link analysis

Award Number: R41GM122169
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: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2019

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Integrated tools for higher order structure determination by cross-link analysis - Summary The use of mass spectrometry (MS) for quantitative protein characterization has increased dramatically; identifying and quantifying thousands of proteins is no longer a heroic task nor is characterizing therapeutic proteins in detail. Due to widely available software, quantitative mass spectrometry has become routine and widely used for addressing questions in basic biology, translational medicine and drug development. MS Methods are now poised to have similar impact on the study of protein-protein interaction and higher order structure (HOS) determination. In particular, crosslinking mass spectrometry, which obtains distance and accessibility constraints from two-ended chemical modifications, is emerging as a powerful tool to map protein-protein interaction interfaces. Recent years have seen large improvements in crosslink mass spectrometry. Yet despite these advances, crosslink analysis is not yet a technique that has found widespread use, due to a range of problems such as the low abundance of crosslinked peptides, unavailability of proprietary reagents, the need for different search algorithms adopted to specific cross-linkers, and the difficulty of reliably characterizing crosslinked peptide spectra. To alleviate these problems and democratize the use of crosslinking, we propose to develop standardized and effective methods for crosslinking in conjunction with sensitive and accurate search algorithms, incorporated into our well-established Byonic search engine. Our algorithms will support almost all commercially available crosslinking chemistries and most major peptide fragmentation methods (ETD, CAD/HCD, EthcD), as well as cleavable and non-cleavable crosslinkers. The near universal applicability and ease-of-use of the software will promote rapid adoption of crosslinking mass spectrometry in academic research and biopharmaceutical development.


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: 2019 ( Subtotal = -$64 )
2019	2017	PROTEIN METRICS INC.	20863 STEVENS CREEK BLVD STE 450	CUPERTINO	CA	95014	SANTA CLARA	USA	Biomedical Research and Research Training	000	1	6/28/2019	NEW	-$64
														Subtotal = -$64

Issue Date FY: 2017 ( Subtotal = $224,870 )
2017	2017	PROTEIN METRICS INC.	1622 SAN CARLOS AVE, SUITE C	SAN CARLOS	CA	94070	SAN MATEO	USA	Biomedical Research and Research Training	000	1	8/29/2017	NEW	$224,870
														Subtotal = $224,870

Grand Total All Awards = $224,806

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Integrated tools for higher order structure determination by cross-link analysis

Award Number: R41GM122169

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: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2019

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