Thursday, July 3, 2025 7/3/2025

Multiscale Modeling of Dynamin Induced Membrane Fission

Award Number: SC2GM131992
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: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Multiscale Modeling of Dynamin Induced Membrane Fission - Multiscale Modeling of Dynamin Induced Membrane Fission The major pathway for recycling the cellular machinery involved in neurotransmission back into the neuron is clathrin mediated endocytosis (CME). The final stage of endocytosis involves the recruitment of the protein dynamin to the neck of the vesicle to cut the membrane and release the vesicle to the interior of the cell. Dynamin forms a helical protein coat around the vesicle neck that ultimately disrupts the lipid membrane and the vesicle is released. Dynamin is able to causes membrane scission by undergoing a large conformational change after catalyzing the hydrolysis of guanosine triphosphate (GTP) to guanosine diphosphate (GDP). Two mechanisms for dynamin induced membrane fission have been proposed. In the constriction model, the explanation is that hydrolysis leads to constriction or twisting of the helical coat, which destabilizes the inner layer of the membrane. In the disassembly model, hydrolysis leads to disassembly of the helical coat, which causes destabilization of the membrane neck and results in fission. In both of these mechanisms, a super-constricted membrane state is achieved prior to membrane scission. Distinguishing between these two models, requires two key major points to be understood: 1) how is the energy released from GTP hydrolysis used by dynamin and 2) how is the super-constricted membrane state reached? We are proposing that an innovative multiscale molecular-modeling approach would be able to compare the two mechanisms directly using computer simulation and determine which is the most energetically favorable. The major innovation in this method is that it maintains the underlying physics and chemistry by combining smaller scale atom-level molecular dynamics simulations with larger scale, low resolution coarse-grained simulations in an iterative way. The overall goal of this work is to develop a multiscale model of dynamin that can be used to determine whether dynamin induced membrane scission occurs via a constriction or protein coat disassembly mechanism. To determine the membrane fission mechanism, we need to determine how the energy released by GTP hydrolysis leads to changes in the structure of dynamin and how dynamin interacts with the membrane. This information can then be combined with simulations of the dynamin protein in solution to develop a model that can be used to directly simulate the fission process. This will help us determine the actual mechanism of membrane scission.


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 = $0 )
2024	2021	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PKWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	3	5/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	3	5/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $164,000 )
2021	2021	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	3	5/28/2021	NON-COMPETING CONTINUATION	$164,000
														Subtotal = $164,000

Issue Date FY: 2020 ( Subtotal = $164,000 )
2020	2020	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	2	5/21/2020	NON-COMPETING CONTINUATION	$164,000
														Subtotal = $164,000

Issue Date FY: 2019 ( Subtotal = $164,000 )
2019	2019	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	1	5/23/2019	NEW	$164,000
														Subtotal = $164,000

Grand Total All Awards = $492,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Multiscale Modeling of Dynamin Induced Membrane Fission

Award Number: SC2GM131992

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: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer