Effect of local stress on accurate modeling of bacterial outer membranes using all-atom molecular dynamics

TL;DR

This study examines how initial membrane stress influences molecular interactions in bacterial outer membranes, revealing that differential tension affects molecule positioning and energy landscapes in asymmetric membranes.

Contribution

It introduces a new perspective on membrane modeling by highlighting the importance of initial stress states and compares different membrane-building protocols.

Findings

Differential stress shifts free energy minima for PQS in membrane leaflets.

Membrane-building protocol impacts initial tension and molecule interaction.

Initial membrane tension influences molecular intercalation behavior.

Abstract

Biological membranes are fundamental components of living organisms that play an undeniable role in their survival. Molecular dynamics (MD) serves as an essential computational tool for studying biomembranes on molecular and atomistic scales. The status quo of MD simulations of biomembranes studies a nanometer-sized membrane patch periodically extended under periodic boundary conditions (PBC). In nature, membranes are usually composed of different lipids in their two layers (referred to as leaflets). This compositional asymmetry imposes a fixed ratio of lipid numbers between the two leaflets in a periodically constrained membrane, which needs to be set appropriately. The widely adopted methods of defining leaflet lipid ratio suffer from the lack of control over the mechanical tension of each leaflet, which could significantly influence research findings. In this study, we investigate the role of membrane-building protocol and the resulting initial stress state on the interaction between small molecules and asymmetric membranes. We model the outer membrane of Pseudomonas aeruginosa bacteria using two different building protocols and probe their interactions with the Pseudomonas Quinolone Signal (PQS). Our results show that differential stress could shift the position of free energy minimum for the PQS molecule between the two leaflets of the asymmetric membrane. This work provides critical insights into the relationship between the initial per-leaflet tension and the spontaneous intercalation of PQS.