Amplification and detection of single molecule conformational fluctuation through a protein interaction network with bimodal distributions

A protein undergoes conformational dynamics with multiple time scales, which results in fluctuating enzyme activities. Recent studies in single molecule enzymology have observe this "age-old" dynamic disorder phenomenon directly. However, the single molecule technique has its limitation. To be able to observe this molecular effect with real biochemical functions {\it in situ}, we propose to couple the fluctuations in enzymatic activity to noise propagations in small protein interaction networks such as zeroth order ultra-sensitive phosphorylation-dephosphorylation cycle. We showed that enzyme fluctuations could indeed be amplified by orders of magnitude into fluctuations in the level of substrate phosphorylation | a quantity widely interested in cellular biology. Enzyme conformational fluctuations sufficiently slower than the catalytic reaction turn over rate result in a bimodal concentration distribution of the phosphorylated substrate. In return, this network amplified single enzyme fluctuation can be used as a novel biochemical "reporter" for measuring single enzyme conformational fluctuation rates.
Comment: 9 pages, 5 figures