COMPUTER-SIMULATION OF THE PHOSPHORYLATION CASCADE CONTROLLING BACTERIAL CHEMOTAXIS

We have developed a computer program that simulates the intracellular reactions mediating the rapid (nonadaptive) chemotactic response of Es cherichia coli bacteria to the attractant aspartate and the repellent Ni2+ ions. The model is built from modular units representing the mole cular components involved, which are each assigned a known value of in tracellular concentration and enzymatic rate constant wherever possibl e. The components are linked into a network of coupled biochemical rea ctions based on a compilation of widely accepted mechanisms but incorp orating several novel features. The computer motor shows the same patt ern of runs, tumbles and pauses seen in actual bacteria and responds i n the same way as living bacteria to sudden changes in concentration o f aspartate or Ni2+. The simulated network accurately reproduces the p henotype of more than 30 mutants in which components of the chemotacti c pathway are deleted and/or expressed in excess amounts and shows a r apidity of response to a step change in aspartate concentration simila r to living bacteria. Discrepancies between the simulation and real ba cteria in the phenotype of certain mutants and in the gain of the chem otactic response to aspartate suggest the existence of additional as y et unidentified interactions in the in vivo signal processing pathway.