Mechanistic insights into hydrophobicity-dependent antimicrobial selectivity of quaternary ammonium poly(oxanorborneneimide) polymers using coarse-grained simulations

The rise of antibiotic resistance to small-molecule drugs has driven the development of materials that directly disrupt bacterial cell membranes. Inspired by antimicrobial peptides (AMPs), synthetic polymers are gaining attention as promising antimicrobial materials because their molecular properties can be tuned to enhance selective killing of bacterial versus mammalian cells. Poly(oxanorborneneimide) (PONI) polymers have exhibited high selectivity against a broad spectrum of bacteria over human cells, depending upon their side chain functionalities. However, the mechanistic basis of this selectivity remains poorly understood, limiting the design of new PONI polymers with enhanced selectivity. In this study, we present a molecular dynamics (MD) simulation framework to investigate PONI-membrane interactions and extract mechanistically relevant descriptors correlated with experimentally determined activities. We model four PONI polymers with side chains of increasing hydrophobicity to un..., , # Mechanistic insights into hydrophobicity-dependent antimicrobial selectivity of quaternary ammonium poly(oxanorborneneimide) polymers using coarse-grained simulations

Dataset DOI: [10.5061/dryad.3j9kd520b](https://doi.org/10.5061/dryad.3j9kd520b)

## Description of the data and file structure

This work presents a generalizable atomistic to coarse-grained parameterization strategy for synthetic poly(oxanorborneneimide) (PONI) polymers in the MARTINI 3 force field for use in polymer-membrane molecular dynamics (MD) simulations with bacterial (*E. coli*, MRSA) and human red blood cell (RBC) membranes. The goal of this study is to provide mechanistic insights on disruption mechanisms of these polymers interacting with bacterial and human membranes to support experimental activity results by Gupta et al. ([doi.org/10.1021/jacs.8b06961)](https://doi.org/10.1021/jacs.8b06961 \"DOI URL\"). All simulations were run with Gromacs 2021.5 patched with PLUMED 2.8.

### Folder Structure

The provide..., ,