In Silico Evolution of Biochemical Log-Response

J Phys Chem B. 2019 Mar 14;123(10):2235-2243. doi: 10.1021/acs.jpcb.8b10974. Epub 2019 Mar 5.

Abstract

Numerous biological systems are known to harbor a form of logarithmic behavior, from Weber's law to bacterial chemotaxis. Such a log-response allows for sensitivity to small relative variations of biochemical inputs over a large range of concentration values. Here we use a genetic algorithm to evolve biochemical networks displaying a logarithmic response. A quasi-perfect log-response implemented by the same core network evolves in a convergent way across our different in silico replications. The best network is able to fit a logarithm over 4 orders of magnitude with an accuracy of the order of 1%. At the heart of this network, we show that a logarithmic approximation may be implemented with one single nonlinear interaction, that can be interpreted either as multisite phosphorylations or as a ligand induced multimerization. We provide an analytical explanation for the effect and exhibit constraints on parameters. Biological log-response might thus be easier to implement than usually assumed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Biochemical Phenomena
  • Computer Simulation*
  • Models, Biological*
  • Models, Chemical*