Accelerating Whole-Cell Simulations of mRNA Translation Using a Dedicated Hardware

Abstract

In recent years, intracellular biophysical simulations have been used with increasing frequency not only for answering basic scientific questions but also in the field of synthetic biology. However, since these models include networks of interaction between millions of components, they are extremely time-consuming and cannot run easily on parallel computers. In this study, we demonstrate for the first time a novel approach addressing this challenge by using a dedicated hardware designed specifically to simulate such processes. As a proof of concept, we specifically focus on mRNA translation, which is the process consuming most of the energy in the cell. We design a hardware that simulates translation in Escherichia coli and Saccharomyces cerevisiae for thousands of mRNAs and ribosomes, which is in orders of magnitude faster than a similar software solution. With the sharp increase in the amount of genomic data available today and the complexity of the corresponding models inferred from them, we believe that the strategy suggested here will become common and can be used among others for simulating entire cells with all gene expression steps.

Thermodynamically-consistent, reduced models of gene regulatory networks

“…Many models completely ignore the energy molecule adenosine triphosphate (ATP) and therefore do not account for the dependence of expression dynamics on energy. This is surprising given that translation consumes four ATP molecules per amino acid (Kempes et al, 2017), making it one of the most energy-consuming processes in a cell (30-75%) (Karr et al, 2012; Shallom et al, 2021). If we are to adequately model gene regulatory networks for the synthetic biology of cell populations, a new modelling approach is needed that accounts for energy while also resulting in models simple enough to be incorporated into large cell populations.…”