Coupling Bulk Phase Separation of Disordered Proteins to Membrane Domain Formation in Molecular Simulations on a Bespoke Compute Fabric
Abstract
:1. Introduction
- We present a simulation-based exploration of the morphological outcomes resulting from the 3D phase separation of intrinsically-disordered proteins near a 2D lipid membrane;
- We describe the novel POETS compute architecture and the algorithm used in POETS-DPD, and demonstrate the power of this approach by simulating selected systems at a fraction of the wall clock time: a 14 cpu-day conventional DPD simulation is completed by POETS-DPD in 8 h, a speedup of more than a factor of 40.
2. Materials and Methods
2.1. Dissipative Particle Dynamics Simulations
2.2. Massively Parallel Event-Based Simulations
- Force calculation
- a
- Sharing: Broadcast each resident bead position and velocity to neighbors;
- b
- Integration: For each received bead, calculate non-bonded DPD and Hookean bond interactions with resident cells;
- c
- AngleForces: Once head and tail beads for an angle bond are received by middle bead, calculate angle forces and broadcast to neighbors (which must include the owner of the angle bond’s head and tail;
- d
- AngleAddition: If an angle force is received and this cell contains the related head or tail bead, apply angle-bond forces to that head/tail.
- Bead movement
- a
- Movement: Apply equations of motion to all beads resident in the cell;
- b
- BeadExit: If any bead leaves the cell, broadcast it to neighbors and remove from resident set;
- c
- BeadEntrance: If a bead is received from a neighbor and its new position is in the current cell, add it to the resident set.
- Go back to step 1 for next step of simulation
3. Results
3.1. Influence of the IDP-Membrane Affinity on the Equilibrium Morphology
3.2. Reversible Coupling of Phase Separation and Domain Formation
3.3. Increasing IDP Length Results in Patchy Domains
3.4. Clustering of Minority Lipids by IDP–Linker Attraction
4. Discussion
- -
- Produce reliable DPD results (agree with published DPD implementation) [53];
- -
- Are useful for practitioners;
- -
- Are competitive in performance with existing single-node systems.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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W | E | B | HA | TA | HB | TB | L | S | |
---|---|---|---|---|---|---|---|---|---|
W | 25 | ||||||||
E | 25 | aEE | |||||||
B | 23 | 25 | 25 | ||||||
HA | 30 | 30 | 30 | 30 | |||||
TA | 75 | 35 | 35 | 35 | 10 | ||||
HB | 30 | aEM | 30 | 30 | 35 | 30 | |||
TB | 75 | 35 | 35 | 35 | 10 | 35 | 10 | ||
L | 30 | 30 | 30 | 30 | 35 | 30 | 35 | 30 | |
S | 30 | aES | 30 | 30 | 35 | 30 | 35 | 30 | 30 |
System | Year | Software | Watts | Nodes | Perf/106 | Perf/Watt |
---|---|---|---|---|---|---|
CPUx1 | 2020 | Osprey-DPD | 250 | 1 | 0.5 | 2000 |
CPUx32 | 2020 | LAMMPS | 500 | 1 | 19.0 | 38,000 |
GPUx1 | 2016 | DL-MESO | 400 | 1 | 23.7 | 59,195 |
GPUx8 | 2016 | DL-MESO | 400 | 32 | 285.7 | 22,321 |
POETS Gen1 | 2011 | POETS-DPD | 200 | 48 | 24.0 | 2500 |
POETS Gen2 | 2022 | POETS-DPD | 250 | 48 | 360.0 | 30,000 |
Target parameters for next generation POETS system: | ||||||
POETS Gen3 | 2025 | POETS-DPD | 250 | 48 | 3600.0 | 300,000 |
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Shillcock, J.C.; Thomas, D.B.; Beaumont, J.R.; Bragg, G.M.; Vousden, M.L.; Brown, A.D. Coupling Bulk Phase Separation of Disordered Proteins to Membrane Domain Formation in Molecular Simulations on a Bespoke Compute Fabric. Membranes 2022, 12, 17. https://doi.org/10.3390/membranes12010017
Shillcock JC, Thomas DB, Beaumont JR, Bragg GM, Vousden ML, Brown AD. Coupling Bulk Phase Separation of Disordered Proteins to Membrane Domain Formation in Molecular Simulations on a Bespoke Compute Fabric. Membranes. 2022; 12(1):17. https://doi.org/10.3390/membranes12010017
Chicago/Turabian StyleShillcock, Julian C., David B. Thomas, Jonathan R. Beaumont, Graeme M. Bragg, Mark L. Vousden, and Andrew D. Brown. 2022. "Coupling Bulk Phase Separation of Disordered Proteins to Membrane Domain Formation in Molecular Simulations on a Bespoke Compute Fabric" Membranes 12, no. 1: 17. https://doi.org/10.3390/membranes12010017