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

## TL;DR

This paper demonstrates how fluctuations in enzyme conformations can be amplified through small protein networks, creating bimodal substrate phosphorylation distributions that serve as in situ reporters of enzyme dynamics.

## Contribution

It introduces a method to detect single enzyme conformational fluctuations by coupling them to noise in protein interaction networks, enabling in situ observation.

## Key findings

- Enzyme fluctuations can be amplified into substrate phosphorylation noise.
- Slow enzyme conformational changes lead to bimodal phosphorylation distributions.
- Network amplification allows in situ measurement of enzyme dynamics.

## Abstract

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.