Thursday, February 19, 2026 2/19/2026

Toward a deeper understanding of allostery and allotargeting by computational approaches

Award Number: R01GM139297
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: 08/05/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

Group Awards By:

View Award Description

Toward a deeper understanding of allostery and allotargeting by computational approaches - Toward a deeper understanding of allostery and allotargeting by computational approaches Understanding allosteric mechanisms of action and their modulation by ligand binding (allo- targeting) gained importance in recent years, as allosteric modulators allow for selective interference with specific protein-protein interactions (PPI) or cellular pathways. Yet, despite the growth of data and methodologies, we still lack a solid understanding of allosteric mechanisms that underlie biological function. We propose that a completely new framework, with focus on the change in structural dynamics rather than changes in the states only, is needed. Furthermore, rather than limiting our attention to transitions between two end-states (e.g. open/closed forms of a protein), one needs to consider the complete ensemble of conformers, and evaluate the effect of intermolecular interactions or mutations vis-à-vis the changes elicited in the conformational landscape. Toward this goal, we propose to develop, implement, and apply innovative computational models and methods that will focus on the essential dynamics of biomolecular systems. Essential dynamics refers to the global modes of motions intrinsically accessible to the overall structure, i.e. they cooperatively engage most, if not all, structural elements of the biological assembly. We propose to: (1) develop, test, and validate an essential site scanning analysis (ESSA) methodology for predicting ‘essential’ sites that dominate the essential dynamics, and discriminating allosteric sites among them (Aim 1), (2) enhance the capability and accuracy of our pathogenicity predictor, RHAPSODY, for evaluating the impact of mutations (single amino acid variants) on biological function, by including in our machine learning algorithm the features derived from global motions of biomolecular systems, the signature dynamics of protein families, and the experimentally resolved PPIs (Aim 2), and (3) develop a hybrid methodology for efficient assessment of conformational landscapes applicable to proteins containing cryptic sites and cryo- EM structures (Aim 3), and finally extend and integrate these new methodologies to enable their efficient translation to biomedical and pharmacological applications. Method development, testing, validation, and further extensions will entail rigorous benchmarking against other methods and/or relevant databases where applicable, in addition to detailed case studies in collaboration with other labs (see support letters from six experimental and one computational collaborator). Integration of the methodologies within our well-established application programming interface ProDy will enable efficient dissemination and wide usage of the new technologies by the broader community.


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: 2024 ( Subtotal = $348,530 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	000	5	4/8/2024	NON-COMPETING CONTINUATION	$313,677
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	001	5	6/17/2024	NON-COMPETING CONTINUATION	$34,853
2024	2022	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	003	3	9/27/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$17,605
2024	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	002	2	9/27/2024	NON-COMPETING CONTINUATION	-$17,605
														Subtotal = $348,530

Issue Date FY: 2023 ( Subtotal = $336,673 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	002	4	9/22/2023	NON-COMPETING CONTINUATION	$348,799
2023	2022	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	001	3	8/25/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$308,807
2023	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	000	2	8/24/2023	NON-COMPETING CONTINUATION	-$320,933
														Subtotal = $336,673

Issue Date FY: 2022 ( Subtotal = $348,183 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	000	2	4/20/2022	NON-COMPETING CONTINUATION	$348,183
														Subtotal = $348,183

Issue Date FY: 2021 ( Subtotal = $344,045 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	8/5/2021	NEW	$344,045
														Subtotal = $344,045

Grand Total All Awards = $1,377,431

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Toward a deeper understanding of allostery and allotargeting by computational approaches

Award Number: R01GM139297

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: 08/05/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer