Protein logic: a statistical mechanical study of signal integration at the single-molecule level

TL;DR

This study uses a statistical mechanical model to demonstrate that single proteins can perform complex logic operations, including XOR, by varying biochemical parameters or forming different receptor combinations, revealing high functional flexibility.

Contribution

It introduces a systematic approach to understanding protein logic, showing that single proteins or receptor combinations can realize diverse logic gates, including XOR, at the molecular level.

Findings

A single heterodimer can realize all 16 logic gates.

Receptor combinations can encode different logic functions.

Cells have high functional flexibility at the single-protein level.

Abstract

Information processing and decision making is based upon logic operations, which in cellular networks has been well characterized at the level of transcription. In recent years however, both experimentalists and theorists have begun to appreciate that cellular decision making can also be performed at the level of a single protein, giving rise to the notion of protein logic. Here we systematically explore protein logic using a well known statistical mechanical model. As an example system, we focus on receptors which bind either one or two ligands, and their associated dimers. Notably, we find that a single heterodimer can realize any of the 16 possible logic gates, including the XOR gate, by variation of biochemical parameters. We then introduce the novel idea that a set of receptors with fixed parameters can encode functionally unique logic gates simply by forming different dimeric combinations. An exhaustive search reveals that the simplest set of receptors (two single-ligand receptors and one double-ligand receptor) can realize several different groups of three unique gates, a result for which the parametric analysis of single receptors and dimers provides a clear interpretation. Both results underscore the surprising functional freedom readily available to cells at the single-protein level.