On Scalable Biomolecular Computers Based on Crosstalked Phosphorylation and Dephosphorylation Pathways Regulated by Rho Family GTPases of Cells

Abstract

Based on the living cell, which is one of the most promising functional materials for building nanobiomachines for massively parallel computation, we propose a new biomolecular computing method based on the signaling pathways of phosphorylation and dephosphorylation switched by kinases and phosphates and regulated by upstream pathways of Rho family GTPases in living cells, a method that differs from the Adleman-Lipton paradigm of DNA computers. The two main merits of this type of biomolecular computing process based on Rho family GTPases are the low cost of pathway control for cells and the high efficiency of the related computing processes, when certain pathway controllers are designed for the engineered pathway units of biomolecular computers. In this paper, we report our latest results on designing experimentally feasible operators and the related computer architecture of the engineered pathways in cells under the regulation of Rho family GTPases for solving large-scale benchmark problems by biomolecular computers, where the crosstalking processes among the pathways, feedback between the downstream and upstream pathways, and interaction with the nuclear receptors of cells are employed. This is a prerequisite for experimental implementation of a computing nanobiomachine based on the signaling pathways of Rho family GTPases in the form of living cells, which can cut costs in the number of controlled molecules for engineered pathways when the interaction ratings of pathways is regulated on the scale of an entire cell.