Linear-Decoupling Enables Accurate Speed and Accuracy Predictions for Copolymerization Processes.

Abstract

Biological processes exhibit remarkable accuracy and speed and can be theoretically explored through various approaches. The Markov-chain copolymerization theory, describing polymer growth kinetics as a Markov chain, provides an exact set of equations to solve for error and speed. Still, due to nonlinearity, these equations are hard to solve. Alternatively, the enzyme-kinetics approach, which formulates a set of linear equations, simplifies the biological processes as transitions between discrete chemical states, but generally, it might not be accurate. Here, we show that the enzyme-kinetic approach can lead to inaccurate fluxes, even for first-order polymerization processes. To address the problem, we propose a simplified linear-decoupling approximation for steady-state probabilities of higher-order copolymer chains under biologically relevant conditions. Our findings demonstrate that the stationary speed and error rate obtained from the linear-decoupling method align closely with exact values from the Markov-chain (nonlinear) approximation. Extending the technique to higher-order processes with proofreading and internal states shows that it works equally well to describe trade-offs between speed and accuracy for DNA replication and transcription elongation. Our work underscores the proposed linear-decoupling approximation's efficacy in addressing the nonlinear behavior of the Markov-chain approach and the enzyme-kinetic approach's limitations, ensuring accurate predictions for high-fidelity biological processes.