# Coarse-Grained Molecular Dynamics Simulations Reveal Potential Role of Cardiolipin in Lateral Organization of Proteorhodopsin

## TL;DR

This study uses simulations to explore how cardiolipin interacts with proteorhodopsin, a light-harvesting protein in marine microbes, and suggests it may influence its function.

## Contribution

The study reveals new residue-specific interactions between cardiolipin and proteorhodopsin using coarse-grained molecular dynamics simulations.

## Key findings

- Electrostatic and nonpolar forces drive specific interactions between cardiolipin and proteorhodopsin.
- Several cardiolipin binding sites were identified near key functional areas of proteorhodopsin.
- Lipid–protein interactions occur on the microsecond time scale and may modulate proton pumping.

## Abstract

Proteorhodopsin (PR)
is a microbial light-harvesting proton pump
protein that is ubiquitous in marine ecosystems and is critical for
biological solar energy conversion. A unique characteristic of PR
is that its function can be directly affected by changes in the surrounding
cellular membrane environment. Cardiolipin (CL) is a commonly found
lipid in mitochondria and bacterial cell membranes and plays a prominent
role in the function of numerous integral membrane proteins, due to
its bulky conical shape and ionizable nature of its headgroup. CL
can directly interact with other microbial rhodopsins and modulate
their function; however, the potential role of CL in the function
of PR is unclear. In this study, we used the MARTINI coarse-grained
force field to characterize the interactions of CL with PR in a model
bilayer via coarse-grained molecular dynamics (MD) simulations. Our
simulations show that both electrostatic and nonpolar forces drive
residue-specific interactions of CL with proteorhodopsin, especially
for the asymmetrical −1 charge state of CL. Several CL binding
sites were identified, with lipid–protein interactions occurring
on the μs time scale. These binding sites are proximal to key
functional areas and regions of oligomerization on PR, suggesting
that CL could play a role in modulating proton pumping of proteorhodopsin.