Interaction-Strength Dependence of CA-Domain Binding Selectivity in a Coarse-Grained Arp2/3 Model
Kwaku Acheampong
Department of Chemical & Biomolecular Engineering, University of Tennessee
The Arp2/3 complex is a central regulator of branched actin-network formation. It is activated by WASP/WAVE-family nucleation-promoting factors whose CA region can contact multiple Arp2/3 surfaces. Because these contacts are transient and partially disordered, a coarse-grained molecular dynamics model was used to ask whether a minimal CA domain can still recover subunit-level recognition within the Arp2/3 complex.
The simulations were performed in LAMMPS at fixed 300 K using a coarse-grained Arp2/3 model and a four-bead CA domain. The validated production workflow used a 100 ns rigid-Langevin baseline with a 10 fs timestep and 1000 fs damping. Contacts were defined as any CA bead within 10 Å of a selected subunit bead. The main analysis focused on Arp2, ArpC1, Arp3, and CA, and the interaction-strength sweep tested KH coefficient scaling at 0.8x, 1.0x, and 1.2x.
The validated 1.0x baseline showed that CA-ArpC1 preference emerges after the early search phase and is driven by persistent local contacts rather than only by closest distance or subunit size. In the late 55-100 ns window, CA-ArpC1 interaction energy was more favorable than CA-Arp2 and CA formed more 10 Å contacts with ArpC1. The interactive trajectory below shows a size-reduced PBC-centered 65-100 ns movie used for the final structural story, including the late frame with maximum ArpC1 contact persistence. Beads that enter the 10 Å CA-contact cutoff are enlarged and highlighted during playback.
Interactive Structure
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10 Å contacts: loading...
Color Legend
- coral/red = CA domain
- gold/orange = ArpC1 region
- teal/blue = Arp2 region
- pale green/gray = Arp3 region
- bright yellow = bead currently within 10 Å of CA
Trajectory file: mse614_kacheamp_01.xyz. The displayed XYZ contains 71 frames from 65-100 ns and 1136 focus-group beads. It is centered on the CA centroid so the binding interface remains visible during playback.
References
Kim, Y.C. and Hummer, G., “Coarse-grained models for simulations of multiprotein complexes: application to ubiquitin binding,” Journal of Molecular Biology, 375(5), 1416–1433 (2008).
Thompson, A.P. et al., “LAMMPS - a flexible simulation tool for particle-based materials modeling at the atomic, meso, and continuum scales,” Computer Physics Communications, 271, 108171 (2022).
Michaud-Agrawal, N. et al., “MDAnalysis: a toolkit for the analysis of molecular dynamics simulations,” Journal of Computational Chemistry, 32, 2319–2327 (2011).
posted: May 2026.
updated: May 2026.