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Molecular Details of Psychoactive Drug Actions

Award Number: R01MH112205
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/06/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

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Molecular Details of Psychoactive Drug Actions - PROJECT SUMMARY: Scientific summary: The 5-HT2-serotonin family of receptors represents essential drug targets for most atypical antipsychotics as well as drugs useful in treating obesity, sleep disorders, psychosis and autistic- spectrum disorders. It is currently unknown how these drugs interact with their target receptors. Here we aim to obtain high resolution structures of 5-HT2-family receptors bound to various transducers (G proteins and arrestins) and biased and unbiased agonists. We will use these structures to prosecute ultra-large-scale docking campaigns (up to 15 billion novel compounds) to discover improved chemical tools for these receptors. These studies are both innovative technically and conceptually by providing an unprecedented understanding of the molecular and atomic details responsible for psychoactive drug actions. Additionally, models which attempt to explain ligand-specific properties of biased signaling from the perspective of ligand-receptor interactions will be tested by a combination of direct structural studies, molecular modeling, docking, site-directed mutagenesis and functional studies. We anticipate that our studies will reveal key ligand-receptor interactions essential for biased signaling for serotonin receptors. Elucidating the molecular details for such interactions provides a template for the structure-guided design of novel therapeutics.


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 = $593,976 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	10	1/30/2026	NON-COMPETING CONTINUATION	$593,976
														Subtotal = $593,976

Issue Date FY: 2025 ( Subtotal = $599,826 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	9	9/17/2025	NON-COMPETING CONTINUATION	$89,974
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	9	3/6/2025	NON-COMPETING CONTINUATION	$509,852
														Subtotal = $599,826

Issue Date FY: 2024 ( Subtotal = $605,561 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	8	8/15/2024	NON-COMPETING CONTINUATION	$60,556
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	8	12/4/2023	NON-COMPETING CONTINUATION	$545,005
														Subtotal = $605,561

Issue Date FY: 2023 ( Subtotal = $611,184 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	7	1/20/2023	NON-COMPETING CONTINUATION	$61,119
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	7	1/12/2023	NON-COMPETING CONTINUATION	$550,065
														Subtotal = $611,184

Issue Date FY: 2022 ( Subtotal = $629,016 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	6	6/27/2022	COMPETING CONTINUATION	$61,516
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	6	1/28/2022	COMPETING CONTINUATION	$567,500
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	003	6	8/25/2022	COMPETING CONTINUATION	$257,972
2022	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	002	5	8/25/2022	NON-COMPETING CONTINUATION	-$257,972
														Subtotal = $629,016

Issue Date FY: 2021 ( Subtotal = $602,028 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	5	1/23/2021	NON-COMPETING CONTINUATION	$602,028
														Subtotal = $602,028

Issue Date FY: 2020 ( Subtotal = $602,028 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	4	12/17/2019	NON-COMPETING CONTINUATION	$541,825
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	4	3/11/2020	NON-COMPETING CONTINUATION	$60,203
														Subtotal = $602,028

Issue Date FY: 2019 ( Subtotal = $602,028 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	3	12/17/2018	NON-COMPETING CONTINUATION	$602,028
														Subtotal = $602,028

Issue Date FY: 2018 ( Subtotal = $602,028 )
2018	2018	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	2	6/1/2018	NON-COMPETING CONTINUATION	$60,203
2018	2018	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	2	12/18/2017	NON-COMPETING CONTINUATION	$541,825
														Subtotal = $602,028

Issue Date FY: 2017 ( Subtotal = $646,715 )
2017	2017	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	1	3/6/2017	NEW	$646,715
2017	2017	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	1	3/8/2017	NEW	$0
														Subtotal = $646,715

Grand Total All Awards = $6,094,390

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Molecular Details of Psychoactive Drug Actions

Award Number: R01MH112205

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/06/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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