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Coupling bulk phase separation of disordered proteins to membrane domain formation in molecular simulations on a bespoke compute fabric

Coupling bulk phase separation of disordered proteins to membrane domain formation in molecular simulations on a bespoke compute fabric
Coupling bulk phase separation of disordered proteins to membrane domain formation in molecular simulations on a bespoke compute fabric
Phospholipid membranes surround the cell and its internal organelles, and their multicomponent nature allows the formation of domains that are important in cellular signalling, the immune system, and bacterial infection. Cytoplasmic compartments are also created by the phase separation of intrinsically disordered proteins into biomolecular condensates. The ubiquity of lipid membranes and protein condensates raises the question of how three-dimensional droplets might interact with two-dimensional domains, and whether this coupling has physiological or pathological importance. Here, we explore the equilibrium morphologies of a dilute phase of a model disordered protein interacting with an ideal-mixing, two-component lipid membrane using coarse-grained molecular simulations. We find that the proteins can wet the membrane with and without domain formation, and form phase separated droplets bound to membrane domains. Results from much larger simulations performed on a novel non-von-Neumann compute architecture called POETS, which greatly accelerates their execution compared to conventional hardware, confirm the observations. Reducing the wall clock time for such simulations requires new architectures and computational techniques. We demonstrate here an inter-disciplinary approach that uses real-world biophysical questions to drive the development of new computing hardware and simulation algorithms.
2077-0375
Brown, Andrew
5c19e523-65ec-499b-9e7c-91522017d7e0
Vousden, Mark
72f20dc7-d350-4982-a680-2d1f9ed5f07f
Bragg, Graeme McLachlan
b5fd19b9-1a51-470b-a226-2d4dd5ff447a
Shillcock, Julian
5fcb7cf0-914e-46d2-b4c8-963fc3f05d77
Beaumont, Jonathan
363f26be-7b4c-4abf-988b-c90c72fdc2f9
Thomas, David Barrie
5701997d-7de3-4e57-a802-ea2bd3e6ab6c
Brown, Andrew
5c19e523-65ec-499b-9e7c-91522017d7e0
Vousden, Mark
72f20dc7-d350-4982-a680-2d1f9ed5f07f
Bragg, Graeme McLachlan
b5fd19b9-1a51-470b-a226-2d4dd5ff447a
Shillcock, Julian
5fcb7cf0-914e-46d2-b4c8-963fc3f05d77
Beaumont, Jonathan
363f26be-7b4c-4abf-988b-c90c72fdc2f9
Thomas, David Barrie
5701997d-7de3-4e57-a802-ea2bd3e6ab6c

Brown, Andrew, Vousden, Mark, Bragg, Graeme McLachlan, Shillcock, Julian, Beaumont, Jonathan and Thomas, David Barrie (2021) Coupling bulk phase separation of disordered proteins to membrane domain formation in molecular simulations on a bespoke compute fabric. Membranes, 12 (1). (doi:10.3390/membranes12010017).

Record type: Article

Abstract

Phospholipid membranes surround the cell and its internal organelles, and their multicomponent nature allows the formation of domains that are important in cellular signalling, the immune system, and bacterial infection. Cytoplasmic compartments are also created by the phase separation of intrinsically disordered proteins into biomolecular condensates. The ubiquity of lipid membranes and protein condensates raises the question of how three-dimensional droplets might interact with two-dimensional domains, and whether this coupling has physiological or pathological importance. Here, we explore the equilibrium morphologies of a dilute phase of a model disordered protein interacting with an ideal-mixing, two-component lipid membrane using coarse-grained molecular simulations. We find that the proteins can wet the membrane with and without domain formation, and form phase separated droplets bound to membrane domains. Results from much larger simulations performed on a novel non-von-Neumann compute architecture called POETS, which greatly accelerates their execution compared to conventional hardware, confirm the observations. Reducing the wall clock time for such simulations requires new architectures and computational techniques. We demonstrate here an inter-disciplinary approach that uses real-world biophysical questions to drive the development of new computing hardware and simulation algorithms.

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Published date: 23 December 2021

Identifiers

Local EPrints ID: 454840
URI: http://eprints.soton.ac.uk/id/eprint/454840
ISSN: 2077-0375
PURE UUID: 138af277-f7c0-497d-bbf0-b511bd8d4e35
ORCID for Graeme McLachlan Bragg: ORCID iD orcid.org/0000-0002-5201-7977
ORCID for David Barrie Thomas: ORCID iD orcid.org/0000-0002-9671-0917

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Date deposited: 24 Feb 2022 21:57
Last modified: 10 Jun 2022 01:57

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Contributors

Author: Andrew Brown
Author: Mark Vousden
Author: Graeme McLachlan Bragg ORCID iD
Author: Julian Shillcock
Author: Jonathan Beaumont
Author: David Barrie Thomas ORCID iD

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