Multiscale Molecular Dynamics of Syntaxin Isoforms: Linking Sequence Variation to SNARE-Mediated Fusion
Dong An, University of Miami
0000-0002-2506-0486
ACCESS Allocation Request BIO250149
| Abstract: | This project will perform both atomistic and coarse-grained (CG) molecular dynamics (MD) simulations to elucidate how Syntaxin (Stx) isoforms (Stx1A, Stx1B, Stx2, Stx3A, Stx3B, and Stx4) regulate SNARE-mediated membrane fusion. We will analyze how sequence variations in the juxtamembrane (JMD) and transmembrane (TMD) domains—especially CC, CV, and VV motifs and additional C-terminus residues—cooperatively affect Syntaxin flexibility, SNARE complex zippering, and membrane fusion kinetics. Simulation sets include: (1) atomistic JMD–TMD systems to assess structural flexibility, (2) CG models to study isoform-specific Syntaxin clustering, and (3) umbrella-sampling simulations to explore Stx isoform-specific SNARE zippering energy landscapes. All simulations will be performed using GROMACS on Bridges-2 (NSF ACCESS) with 16 or 64 CPU cores for CG or AA simulations, respectively within 2–10 days per simulation. All simulation data will temporarily stored in ~200 GB storage. The requested resources will provide essential insights into isoform-specific Syntaxin regulation of neurotransmission and hormone secretion. | |
Allocations:
| 2025 | PSC Bridges-2 Regular Memory (PSC Bridges-2 RM) | 1,451,004.61 Core-hours |
| 2025 | PSC Bridges-2 Storage (PSC Ocean) | 500.0 GB |
| The estimated value of these awarded resources is $17,426.06. The allocation of these resources represents a considerable investment by the NSF in advanced computing infrastructure for the U.S. The dollar value of the allocation is estimated from the NSF awards supporting the allocated resources. | ||
| 2025 | PSC Bridges-2 Regular Memory (PSC Bridges-2 RM) | 399,000.0 Core-hours |
| 2025 | PSC Bridges-2 Storage (PSC Ocean) | 100.0 GB |
| The estimated value of these awarded resources is $4,790.80. The allocation of these resources represents a considerable investment by the NSF in advanced computing infrastructure for the U.S. The dollar value of the allocation is estimated from the NSF awards supporting the allocated resources. | ||
Other Titles:
Click to show/hide prior titles »| Exploring Syntaxin Isoform-Specific Effects on Membrane Reshaping and Protein–Lipid Interactions |