Simulation of stochastic network dynamics via entropic matching

The simulation of complex stochastic network dynamics arising, for instance, from models of coupled biomolecular processes remains computationally challenging. Often, the necessity to scan a models' dynamics over a large parameter space renders full-fledged stochastic simulations impractical, motivating approximation schemes. Here we propose an approximation scheme which improves upon the standard linear noise approximation while retaining similar computational complexity. The underlying idea is to minimize, at each time step, the Kullback-Leibler divergence between the true time evolved probability distribution and a Gaussian approximation (entropic matching). This condition leads to ordinary differential equations for the mean and the covariance matrix of the Gaussian. For cases of weak nonlinearity, the method is more accurate than the linear method when both are compared to stochastic simulations.Comment: 23 pages, 6 figures; significantly revised versio

Coupled dynamics of RNA folding and nanopore translocation

The translocation of structured RNA or DNA molecules through narrow pores necessitates the opening of all base pairs. Here, we study the interplay between the dynamics of translocation and base-pairing theoretically, using kinetic Monte Carlo simulations and analytical methods. We find that the transient formation of basepairs that do not occur in the ground state can significantly speed up translocation.Comment: 4 pages, 3 figures, to appear in Physical Review Letter

The prebiotic evolutionary advantage of transferring genetic information from RNA to DNA.

In the early 'RNA world' stage of life, RNA stored genetic information and catalyzed chemical reactions. However, the RNA world eventually gave rise to the DNA-RNA-protein world, and this transition included the 'genetic takeover' of information storage by DNA. We investigated evolutionary advantages for using DNA as the genetic material. The error rate of replication imposes a fundamental limit on the amount of information that can be stored in the genome, as mutations degrade information. We compared misincorporation rates of RNA and DNA in experimental non-enzymatic polymerization and calculated the lowest possible error rates from a thermodynamic model. Both analyses found that RNA replication was intrinsically error-prone compared to DNA, suggesting that total genomic information could increase after the transition to DNA. Analysis of the transitional RNA/DNA hybrid duplexes showed that copying RNA into DNA had similar fidelity to RNA replication, so information could be maintained during the genetic takeover. However, copying DNA into RNA was very error-prone, suggesting that attempts to return to the RNA world would result in a considerable loss of information. Therefore, the genetic takeover may have been driven by a combination of increased chemical stability, increased genome size and irreversibility

Quantifying the benefit of a proteome reserve in fluctuating environments.

The overexpression of proteins is a major burden for fast-growing bacteria. Paradoxically, recent characterization of the proteome of Escherichia coli found many proteins expressed in excess of what appears to be optimal for exponential growth. Here, we quantitatively investigate the possibility that this overexpression constitutes a strategic reserve kept by starving cells to quickly meet demand upon sudden improvement in growth conditions. For cells exposed to repeated famine-and-feast cycles, we derive a simple relation between the duration of feast and the allocation of the ribosomal protein reserve to maximize the overall gain in biomass during the feast

Kinetic Accessibility of Buried DNA Sites in Nucleosomes

Using a theoretical model for spontaneous partial DNA unwrapping from histones, we study the transient exposure of protein-binding DNA sites within nucleosomes. We focus on the functional dependence of the rates for site exposure and reburial on the site position, which is measurable experimentally and pertinent to gene regulation. We find the dependence to be roughly described by a random walker model. Close inspection reveals a surprising physical effect of flexibility-assisted barrier crossing, which we characterize within a toy model, the "semiflexible Brownian rotor."Comment: final version as published in Phys. Rev. Let