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Enhancing crystallization with binding partners, symmetry and diversity

Award Number: P01GM098177
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: 06/01/2012
PERIOD OF PERFORMANCE END DATE: 05/31/2017

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Enhancing crystallization with binding partners, symmetry and diversity - DESCRIPTION (provided by applicant): The bottleneck in structure determination by X-ray crystallography is crystallization, where roughly 70% of purified proteins fail. Two major reasons proteins fail to enter the crystalline state are having too few lattice contacts, and having multipe conformations, often the result of missing partner proteins. The purpose of this project is to overcome barriers to crystallization. The key overall ideas in this project are that crystallizatio of a macromolecule or complex can be improved by (1) presenting this macromolecule in a form that is highly suitable for crystallization and (2) creating many different forms of the macromolecule. These themes of optimizing crystallizability and variation are central to all three components of this projects. The innovation new methods we propose to develop will use a combination of natural binding partners and binding modules to improve crystallization of a target macromolecule by (1) creating many different forms of a molecule to crystallize and (2) finding a natural partner macromolecule that stabilizes and enhances the crystallizability of a target macromolecule. Many forms of a molecule will be created using a panel of symmetry-forming modules that can be linked to the target molecule. These modules will be antibody- or green fluorescent protein-based. Natural binding partners will be found with a combination of novel bioinformatics and experimental approaches. The transformative methods are scalable, synergistic, and offer the potential of accelerating results in both structural biology and structual genomics by providing a molecular toolkit for diversifying the potential crystallization arrangements and symmetries of targeted proteins. This program project will be carried out by our UCLA/ Los Alamos team as three tightly integrated subprojects, each involving researchers from both UCLA and Los Alamos. This work will lead to methods that will be used by the structural biology community to determine structures of proteins that will increase our understanding of human health and our ability to cure human disease.


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: 2018 ( Subtotal = -$6,973 )
2018	2015	LOS ALAMOS NATIONAL SECURITY, LLC	BIKINI ATOLL RD SM 30	LOS ALAMOS	NM	87545	LOS ALAMOS	USA	Biomedical Research and Research Training	000	4	11/11/2017	NON-COMPETING CONTINUATION	-$6,973
														Subtotal = -$6,973

Issue Date FY: 2015 ( Subtotal = $1,196,491 )
2015	2015	LOS ALAMOS NATIONAL SECURITY LLC	4200 WEST JEMEZ ROAD	LOS ALAMOS	NM	87544	LOS ALAMOS	USA	Biomedical Research and Research Training	000	4	5/18/2015	NON-COMPETING CONTINUATION	$1,196,491
														Subtotal = $1,196,491

Issue Date FY: 2014 ( Subtotal = $1,196,491 )
2014	2014	LOS ALAMOS NATIONAL SECURITY LLC	4200 WEST JEMEZ ROAD	LOS ALAMOS	NM	87544	LOS ALAMOS	USA	Biomedical Research and Research Training	000	3	6/4/2014	NON-COMPETING CONTINUATION	$1,196,491
														Subtotal = $1,196,491

Issue Date FY: 2013 ( Subtotal = $1,154,613 )
2013	2013	LOS ALAMOS NATIONAL SECURITY LLC	4200 WEST JEMEZ ROAD	LOS ALAMOS	NM	87544	LOS ALAMOS	USA	Biomedical Research and Research Training	000	2	5/28/2013	NON-COMPETING CONTINUATION	$1,154,613
														Subtotal = $1,154,613

Issue Date FY: 2012 ( Subtotal = $1,196,491 )
2012	2012	LOS ALAMOS NATIONAL SECURITY LLC	4200 WEST JEMEZ ROAD	LOS ALAMOS	NM	87544	LOS ALAMOS	USA	Biomedical Research and Research Training	000	1	5/21/2012	NEW	$1,196,491
														Subtotal = $1,196,491

Grand Total All Awards = $4,737,113

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Enhancing crystallization with binding partners, symmetry and diversity

Award Number: P01GM098177

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: 06/01/2012

PERIOD OF PERFORMANCE END DATE: 05/31/2017

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