Molecular Simulations of Gram-Negative Bacterial Membranes Come of Age

Abstract

Gram-negative bacteria are protected by a multicompartmental molecular architecture known as the cell envelope that contains two membranes and a thin cell wall. As the cell envelope controls influx and efflux of molecular species, in recent years both experimental and computational studies of such architectures have seen a resurgence due to the implications for antibiotic development. In this article we review recent progress in molecular simulations of bacterial membranes. We show that enormous progress has been made in terms of the lipidic and protein compositions of bacterial systems. The simulations have moved away from the traditional setup of one protein surrounded by a large patch of the same lipid type toward a more bio-logically representative viewpoint. Simulations with multiple cell envelope components are also emerging. We review some of the key method developments that have facilitated recent progress, discuss some current limitations, and offer a perspective on future directions.

Lipid-mediated antimicrobial resistance: a phantom menace or a new hope?

“…When combined with recent advances in cryo-EM structural elucidation, structure-based drug design, as well as improved computational hardware and algorithms, these advances allow for the development of detailed molecular models that can reveal the mechanisms that underpin lipid-mediated AMR in bacteria. Molecular simulation of bacterial membranes, and biological membranes in general, has advanced significantly over the past 20 years, with larger, more complex and more realistic simulations becoming feasible (Marrink et al 2019 ; Wilson et al 2020b ; Im and Khalid 2020 ). Advances in forcefields, particularly the CHARMM atomistic forcefield and MARTINI coarse-grained forcefield (Marrink et al 2004 , 2007 ; Wu et al 2014 ; Lee et al 2019a ), coupled with increasing hardware capabilities and improvements in simulation tooling, has enabled simulations of membranes approaching realistic chemical diversity in constituent protein and lipid components (Ingólfsson et al 2014 , 2017 ; Reddy et al 2015 ; Wilson et al 2020a , 2021 ).…”

Antibacterial Activity of Some Terrestrial Gastropods From Egypt Against Staphylococcus Aureus and Escherichia Coli

“…Also, no antibacterial activity of Mytilus galloprovincialis haemolymph against E. coli was detected [26] . This could be explained by that the resistance of E. coli (Gram-negative) bacteria was due to their complex wall structure (proteinlipopolysaccharides), which can exclude most of the active compounds [27] . Ramli et al [15] and Othman at al.…”

CHARMM‐GUI Drude prepper for molecular dynamics simulation using the classical Drude polarizable force field

“…Escherichia coli O176 O‐antigen oligosaccharide : O‐antigen polysaccharides constitutes part of the lipopolysaccharide molecule present in the outer membrane of Gram‐negative bacteria, 119 which have diverse chemical compositions even within a single species 120 . In a previous study, Patel et al studied the conformational preferences of an Escherichia coli O176 O‐antigen oligosaccharide at the atomic level using NMR spectroscopy and MD simulations 121 .…”