Sensitivity of Phage Lambda upon Variations of the Gibbs Free Energy

TL;DR

This study assesses how uncertainties in DNA binding energies affect the activity of regulatory proteins in bacteriophage lambda, demonstrating that despite variability, the genetic switch remains functionally feasible.

Contribution

It introduces a computational scattering method to evaluate the impact of experimental error on protein-DNA binding energies and promoter activities in lambda phage regulation.

Findings

Promoter activities show >20% variability due to experimental error.

Despite variability, the genetic switch remains distinguishable and functional.

A new compact data presentation method for repressor and Cro proteins.

Abstract

We investigate the sensitivity of production rates (activities) of the regulatory proteins CI (repressor) and Cro at the right operator (O_R}) of bacteriophage lambda. The DNA binding energies of CI, Cro, and RNA polymerase are perturbed to check the uncertainty of the activity, due to the experimental error, by means of a computational scattering method according to which the binding energies are simultaneously chosen at random around the literature values, with a width corresponding to the experimental error. In a grand canonical ensemble, with the randomly drawn protein-DNA binding energies as input, we calculate the corresponding activities of the promoters P_RM and P_R. By repeating this procedure we obtain a mean value of the activity that roughly corresponds to wild-type (unperturbed) activity. The standard deviation emerging from this scheme, a measure of the sensitivity due to experimental error, is significant (typically > 20% relative to wild-type activity), but still the promoter activities are sufficiently separated to make the switch feasible. We also suggest a new compact way of presenting repressor and Cro data.