SIMCROST: A Simulator for Understanding the Spatial Regulation in Cross‐Membrane Signal Transduction

Cross‐membrane signal transduction is the initial step in cell‐signaling pathways that enable responses to specific stimuli. It is not a stochastic event but a highly coordinated process that unfolds through multiple layers of spatiotemporal regulation. The detailed molecular mechanisms and functional implications of these regulations during cross‐membrane signal transduction, however, are not completely understood. To tackle this problem, we present a hybrid simulation method called SIM ulator of CRO ss‐membrane S ignal T ransduction (SIMCROST) that incorporates both spatial diffusions of proteins and the kinetics of their interactions to mimic the process ranging from ligand–receptor interactions on the plasma membrane to the assembly of scaffold proteins in the cytoplasm. We tested SIMCROST on a hypothetical system, using currently available experimental evidence of receptor tyrosine kinase (RTK) as a prototype. Our simulation results validate SIMCROST as a powerful tool for elucidating how structural patterns and spatial dynamics regulate physiological cellular responses, providing a mechanistic explanation for previous experimental observations regarding the nonstochastic nature of signal transduction. Moreover, SIMCROST can be potentially applied to any system of cell‐signaling pathways and serve as a useful addition to current experimental approaches.