# Titratable residues that drive RND efflux: Insights from molecular simulations

## TL;DR

This paper reviews computational studies on how RND efflux pumps in bacteria use protons to expel antibiotics, focusing on the number of protons involved in each cycle.

## Contribution

The paper provides a comprehensive review of recent computational insights into the proton stoichiometry of RND efflux pumps.

## Key findings

- Computational studies have been crucial in understanding proton transfer in RND efflux pumps.
- The number of protons transferred per conformational cycle remains a key focus of research.
- Structural biology methods face challenges in studying proton movement, making simulations essential.

## Abstract

The resistance–nodulation–division efflux machinery confers antimicrobial resistance to Gram-negative bacteria by actively pumping antibiotics out of the cell. The protein complex is powered by proton motive force; however, the proton transfer mechanism itself and indeed even its stoichiometry is still unclear. Here we review computational studies from the last decade that focus on elucidating the number of protons transferred per conformational cycle of the pump. Given the difficulties in studying proton movement using even state-of-the-art structural biology methods, the contributions from computational studies have been invaluable from a mechanistic perspective.