# TORCphysics: a physical model of DNA-topology-controlled gene expression

**Authors:** Victor Velasco-Berrelleza, Penn Faulkner Rainford, Aalap Mogre, Craig J Benham, Charles J Dorman, Carsten Kröger, Susan Stepney, Sarah A Harris

PMC · DOI: 10.1093/nar/gkag126 · Nucleic Acids Research · 2026-02-18

## TL;DR

This paper introduces a physical model called TORCphysics that simulates how DNA topology influences gene expression.

## Contribution

The novelty of TORCphysics is its versatility in allowing users to define different activity models for various proteins and binding sites.

## Key findings

- Gene expression profiles are influenced by gene circuit design, including gene location and topological barriers.
- The model computes DNA output based on constrained genome architecture under biological conditions.
- TORCphysics provides a flexible framework for simulating gene regulation mechanisms.

## Abstract

DNA superhelicity and transcription are intimately related because changes to DNA topology can influence gene expression and vice versa. Information is transferred through the modulation of local DNA torsional stress, where the expression of one gene may influence the superhelical level of neighbouring genes, either promoting or repressing their expression. In this work, we introduce a one-dimensional physical model that simulates supercoiling-mediated regulation. This TORCphysics model takes as input a genome architecture represented either by a plasmid or chromosomal DNA sequence with ends constrained under specific biological conditions and computes the molecule’s output. Our findings demonstrate that the expression profiles of genes are directly influenced by the gene circuit design, including gene location, the positions of topological barriers, promoter sequences, and topoisomerase activity. The novelty that TORCphysics offers is versatility, where users can define distinct activity models for different types of proteins and protein-binding sites. The aim of this research is to establish a flexible framework for developing physical simulations of gene circuits to deepen our comprehension of the intricate mechanisms involved in gene regulation.

Graphical AbstractFor image description, please refer to the figure legend and surrounding text.

## Full-text entities

- **Chemicals:** ADP (MESH:D000244), ATP (MESH:D000255), NAPs (-)
- **Species:** Escherichia coli (E. coli, species) [taxon 562]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12914363/full.md

## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914363/full.md

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Source: https://tomesphere.com/paper/PMC12914363