Towards Long-Timescale Molecular Dynamics of Cytoplasmic Subdomains: Modeling Crowding, Polydispersity, and Pairwise Interactions
The cell cytoplasm is a crowded environment that is host to a variety of macromolecules. The motions of these molecules deviate from simple Brownian statistics, yet the physical origin of the heavy-tailed, non-Gaussian step-length distributions reported in the live-cell experiments remains unclear....
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| Tipo de recurso: | tesis de maestría |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Valladolid |
| Repositorio: | UVaDOC. Repositorio Documental de la Universidad de Valladolid |
| OAI Identifier: | oai:uvadoc.uva.es:10324/77887 |
| Acceso en línea: | https://uvadoc.uva.es/handle/10324/77887 |
| Access Level: | acceso abierto |
| Palabra clave: | Diffusion coefficient MSD Cytoplasm Molecular Dynamics Polydispersity |
| Sumario: | The cell cytoplasm is a crowded environment that is host to a variety of macromolecules. The motions of these molecules deviate from simple Brownian statistics, yet the physical origin of the heavy-tailed, non-Gaussian step-length distributions reported in the live-cell experiments remains unclear. This work presents a fully automated, colloidal molecular dynamics framework in LAMMPS to assert whether size polydispersity by itself can cause such heterogeneity. Proteins and complexes are represented as rigid, colloidal spheres (log-normal distributed radii from 2 to 40 nm) and are packed at 25-45% volume fractions and evolved for up to 0.5 ms with Langevin dynamics. A Python code is developed that fully automates the process of creating a simulation setup, from generating overlap-free initial configurations, to calculating all N(N + 1)/2 cutoff distances (where N is the number of different radii present in the simulation) for the colloid pair coefficients. Strong-scaling benchmark and efficient neighbor list parameters optimization resulted in reaching a performance of ≈ 420 µs of simulation time per one day of real time. When the colloid potential Hamaker constant is set to 10−5 eV the colloids behave as hard spheres: diffusion coefficients follow the inverse-radius Stokes-Einstein trend and retain Brownian motion statistics across all crowding levels. Raising A above 0.1 eV introduces short-range attraction that leaves small particles almost unchanged but doubles the long-time diffusivity of the largest particles and, crucially, produces the exponential tails in the log-probability of the step-lengths - mirroring the experimental results. Thus, polydispersity and steric crowding alone insufficient. Weak inter-colloidal attractions are likely essential for the observed cytoplasmic heterogeneity |
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