Thermodynamic restrictions on evolutionary optimization of transcription factor proteins

TL;DR

This paper models how conformational fluctuations in transcription factor proteins can be optimized thermodynamically to minimize binding time, suggesting bacteria operate near this optimal regime for efficient gene regulation.

Contribution

It introduces a simple model linking conformational state spectrum to binding efficiency, revealing thermodynamic limits on protein-DNA interaction times.

Findings

Optimal conformational spectrum matches target recognition rate.

Binding time approaches thermodynamic limit in bacteria.

Conformational fluctuations are tuned for efficiency.

Abstract

Conformational fluctuations are believed to play an important role in the process by which transcription factor proteins locate and bind their target site on the genome of a bacterium. Using a simple model, we show that the binding time can be minimized, under selective pressure, by adjusting the spectrum of conformational states so that the fraction of time spent in more mobile conformations is matched with the target recognition rate. The associated optimal binding time is then within an order of magnitude of the limiting binding time imposed by thermodynamics, corresponding to an idealized protein with instant target recognition. Numerical estimates suggest that typical bacteria operate in this regime of optimized conformational fluctuations.