Fluctuations in Mass-Action Equilibrium of Protein Binding Networks

TL;DR

This paper analyzes how fluctuations in protein binding networks are influenced by network connectivity and protein abundance, revealing conditions that amplify spontaneous fluctuations and their dependence on network structure.

Contribution

It introduces a statistical mechanics approach to quantify fluctuations in protein binding networks and explores their dependence on network connectivity and protein abundance.

Findings

Fluctuations can be power-law amplified in connected networks.

Fluctuation strength correlates positively with network connectivity.

Fluctuation amplitude inversely correlates with complex abundance.

Abstract

We consider two types of fluctuations in the mass-action equilibrium in protein binding networks. The first type is driven by relatively slow changes in total concentrations (copy numbers) of interacting proteins. The second type, to which we refer to as spontaneous, is caused by quickly decaying thermodynamic deviations away from the equilibrium of the system. As such they are amenable to methods of equilibrium statistical mechanics used in our study. We investigate the effects of network connectivity on these fluctuations and compare them to their upper and lower bounds. The collective effects are shown to sometimes lead to large power-law distributed amplification of spontaneous fluctuations as compared to the expectation for isolated dimers. As a consequence of this, the strength of both types of fluctuations is positively correlated with the overall network connectivity of proteins forming the complex. On the other hand, the relative amplitude of fluctuations is negatively correlated with the abundance of the complex. Our general findings are illustrated using a real network of protein-protein interactions in baker's yeast with experimentally determined protein concentrations.