High-Performance Whole-Cell Simulation Exploiting Modular Cell Biology Principles

One of the grand challenges of this century is modeling and simulating a whole cell. Extreme regulation of an extensive quantity of model and simulation data during whole-cell modeling and simulation renders it a computationally expensive research problem in systems biology. In this article, we present a high-performance whole-cell simulation exploiting modular cell biology principles. We prepare the simulation by dividing the unicellular bacterium, Escherichia coli (E. coli), into subcells utilizing the spatially localized densely connected protein clusters/modules. We set up a Brownian dynamics-based parallel whole-cell simulation framework by utilizing the Hamiltonian mechanics-based equations of motion. Though the velocity Verlet integration algorithm possesses the capability of solving the equations of motion, it lacks the ability to capture and deal with particle-collision scenarios. Hence, we propose an algorithm for detecting and resolving both elastic and inelastic collisions and subsequently modify the velocity Verlet integrator by incorporating our algorithm into it. Also, we address the boundary conditions to arrest the molecules' motion outside the subcell. For efficiency, we define one hashing-based data structure called the cellular dictionary to store all of the subcell-related information. A benchmark analysis of our CUDA C/C++ simulation code when tested on E. coli using the CPU-GPU cluster indicates that the computational time requirement decreases with the increase in the number of computing cores and becomes stable at around 128 cores. Additional testing on higher organisms such as rats and humans informs us that our proposed work can be extended to any organism and is scalable for high-end CPU-GPU clusters.