UC Irvine

On the surface of T Cells, large transmembrane molecules such as CD45 are distributed across thesurface. However, during engagement with antigen-presenting cells, these proteins are noticeably absent from the region surrounding the T-Cell receptors (TCR) involved. Computer simulations can aid in studying these processes. However, simulations of spatiotemporal dynamics of protein reorganizations on cell surfaces can be computationally expensive when they involve rare events – that is, when processes of interest are slow relative to other relevant timescales in the system. To better understand the process of TCR triggering, we build a biochemical simulator that imple- ments the rare event sampling method Weighted Ensemble together with particle-based reaction diffusion simulation. We investigate how two simple processes, oligomerization and formation of close-contacts, can impact these otherwise rare events. While working with Weighted Ensemble, we further investigated the properties of the outputs from rare event simulations. We invetigated how best to quantify error from Weighted Ensemble simulations, developed metrics toward pre- diction of accuracy, and tested Weighted Ensemble specific metaparameters’ impact on simulation output. This work finds that the processes of oligomerization and close-contact formation can both have drastic impacts on molecular evacuation rates, but even the reduced evacuation times are still unrealistically long, suggesting that a yet-to-be-described mechanism drives evacuation. Further- more, we reveal key characteristics of Weighted Ensemble simulation traces and suggest future methods of exploring these characteristics.