# Multiscale Modeling of Dynamin Induced Membrane Fission

> **NIH NIH SC2** · ST. JOHN'S UNIVERSITY · 2020 · $164,000

## Abstract

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.

## Key facts

- **NIH application ID:** 9934252
- **Project number:** 5SC2GM131992-02
- **Recipient organization:** ST. JOHN'S UNIVERSITY
- **Principal Investigator:** Francisco X. Vazquez
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $164,000
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934252

## Citation

> US National Institutes of Health, RePORTER application 9934252, Multiscale Modeling of Dynamin Induced Membrane Fission (5SC2GM131992-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934252. Licensed CC0.

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